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Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

BackgroundBariatric surgery alters bile acid metabolism, which contributes to post-operative improvements in metabolic health. However, the mechanisms by which bariatric surgery alters bile acid metabolism are incompletely defined. In particular, the role of the gut microbiome in the effects of bariatric surgery on bile acid metabolism is incompletely understood. Therefore, we sought to define the changes in gut luminal bile acid composition after vertical sleeve gastrectomy (VSG).MethodsBile acid profile was determined by UPLC-MS/MS in serum and gut luminal samples from VSG and sham-operated mice. Sham-operated mice were divided into two groups: one was fed ad libitum, while the other was food-restricted to match their body weight to the VSG-operated mice.ResultsVSG decreased gut luminal secondary bile acids, which was driven by a decrease in gut luminal deoxycholic acid concentrations and abundance. However, gut luminal cholic acid (precursor for deoxycholic acid) concentration and abundance did not differ between groups. Therefore, the observed decrease in gut luminal deoxycholic acid abundance after VSG was not due to a reduction in substrate availability.ConclusionVSG decreased gut luminal deoxycholic acid abundance independently of body weight, which may be driven by a decrease in gut bacterial bile acid metabolism.

Bile acid (BA) is one of the main active components of bile and has multiple isomers, the structure or content of its isomers often changes due to diseases and other health problems; thus, the accurate detection of BA isomers is very important. In this study, two groups of BA isomers of glycine-conjugated BAs and taurine-conjugated BAs were simultaneously separated and quantitatively analyzed by ion mobility mass spectrometry (IM-MS). Especially, baseline mobility separation between the isomers was achieved by the formation of binary complexes via simple interaction with spiramycin (SPM), for which a separation resolution (Rp-p) of 1.96 was reached. Moreover, BA isomers were quantitatively analyzed, and the limit of detection (LOD) of absolute quantification for TCDCA/TUDCA and GUDCA/GCDCA/GHDCA was 0.514 and 0.611 ng∙mL−1, respectively; the LODs for molar ratio ranges of relative quantification for TCDCA/TUDCA, GUDCA/GHDCA, and GCDCA/GHDCA were 1:18–30:1, 1:18–21:1, and 1:19–21:1, respectively. Additionally, BA isomers analyzed in pig bile powder and bear bile powder were measured, which were in good consistency with those labeled, revealing the differences in BA composition and content between the two powders. Finally, BA detection and recovery analyses were performed on serum samples, with a recovery rate of ≥73.69%, RSD of ≤6.8%, and SR (standard deviation of recoveries, the degree of difference between measured values and average recovery) of ≤1.27. Due to the simple, rapid, and lack of need for complex sample preparation and chromatographic separation, the proposed method can be an effective method for BA detection in practical samples. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsDiarrhoea is one of the most serious complications in hereditary ATTR (ATTRv) amyloidosis. However, its precise pathomechanism remains unknown. The present study investigated the involvement of bile acid in diarrhoea along with the therapeutic effect of colestimide, a bile acid sequestrant, in ATTRv amyloidosis.We prospectively enrolled 19 ATTRv amyloidosis patients (9 with refractory diarrhoea and 10 without diarrhoea) and 20 healthy individuals for measurements of serum 7a-hydroxy-4-cholesten-3-one (C4) levels. The patients with diarrhoea were then treated with oral colestimide (1.5 g twice daily) for 28 days. The frequency of diarrhoea and C4 level were evaluated before and after colestimide treatment.Mean serum C4 level was significantly higher in ATTRv patients with diarrhoea (62.3 ng/mL) than in ATTRv patients without diarrhoea (24.0 ng/mL, p = 0.03). Colestimide treatment significantly decreased mean diarrhoea frequency (pre-treatment period: 9.1 times/week, colestimide treatment period, 6.6 times/week, p = 0.04) and increased mean C4 level (before treatment: 66.2 ng/mL, after treatment: 187.1 ng/mL, p = 0.02).Bile acid status was significantly associated with diarrhoea in ATTRv amyloidosis. Colestimide and other bile acid sequestrants may reduce diarrhoea frequency in afflicted patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Materials & Methods Results Discussion & Conclusion Drug‐induced liver injury represents a critical public health issue, marked by unpredictable and potentially severe adverse reactions to medications, herbal products or dietary supplements.Acetaminophen is notably a leading cause of hepatotoxicity, impacting over one million individuals worldwide.Extensive research has elucidated the intricate mechanisms driving APAP‐induced liver injury, emphasising the significant roles of endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction and cell death.These insights pave the way for innovative therapeutic strategies, including the use of magnesium, bile acids, microbiota modulation and mesenchymal stem cells.This review explores into these pathological mechanisms, proposing viable therapeutic interventions for patients suffering from APAP‐induced liver injury. [ABSTRACT FROM AUTHOR]

Background: Given the high prevalence of gestational diabetes mellitus and its significant impact on maternal and neonatal health, identifying reliable biomarkers for prediction and diagnosis is essential. The increased incidence of gestational diabetes mellitus among patients with intrahepatic cholestasis of pregnancy suggests a possible association between serum total bile acid levels and gestational diabetes mellitus. This study evaluated the relationship between total bile acid levels and gestational diabetes mellitus incidence. Methods: A systematic search was performed on February 19, 2024, for studies examining the association between total bile acid levels and gestational diabetes mellitus incidence in both the general pregnant population and patients diagnosed with intrahepatic cholestasis of pregnancy. Meta-analyses were conducted to compare pooled total bile acid levels between patients with and without gestational diabetes mellitus, as well as to assess gestational diabetes mellitus prevalence in patients with mild (10 ≤ total bile acid < 40 µmol/L) vs. moderate-to-severe intrahepatic cholestasis of pregnancy (total bile acid ≥ 40 µmol/L). Results: 15 observational studies involving 7,238 pregnant women were systematically reviewed. Our meta-analysis found significantly higher serum total bile acid levels in women diagnosed with gestational diabetes mellitus compared to controls in the general population (Hedge's g = 0.29 [0.03,0.54]). However, subgroup analysis indicated that total bile acid levels were only significantly higher in patients measured earlier in pregnancy, before the gestational diabetes mellitus diagnosis, compared to healthy controls (Hedge's g = 0.48 [0.33,0.64]), while no significant difference in total bile acid levels was observed when measurements were taken after the gestational diabetes mellitus diagnosis (Hedge's g = 0.00 [-0.26,0.27]). Additionally, we found that the prevalence of gestational diabetes mellitus was significantly lower in patients with mild intrahepatic cholestasis of pregnancy compared to those with moderate-to-severe intrahepatic cholestasis of pregnancy (Log odds ratio=-0.56 [-0.95,-0.17]). Conclusions: This study highlights a complex relationship between serum total bile acid levels and gestational diabetes mellitus incidence, influenced by the timing of measurement. Elevated total bile acid levels early in pregnancy may predict gestational diabetes mellitus, but its diagnostic value may decline later in pregnancy. Trial registration: The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 3/3/2024 under CRD42024516164. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota‐derived metabolites in PD were small‐scale and post‐diagnosis, raising concerns about reverse causality.Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.A nested case–control study within the prospective EPIC4PD cohort, measured pre‐diagnostic plasma microbial metabolites using untargeted metabolomics.Thirteen microbial metabolites were identified nominally associated with PD risk (P‐value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD‐associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals.Changes in microbial metabolites may represent a pre‐diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies have increasingly demonstrated that a multiplatform water environment combined with lard gavage is an effective method for establishing a mouse model of diarrhea. However, the interactions between intestinal microorganisms and diarrhea, as well as the relationships among energy metabolism, fluid balance, and gastrointestinal function in this model, remain poorly understood. Methods: Building on previous research, this study aimed to optimiz and replicate a multiplatform water environment combined with a lard gavage model. Male Kunming mice, free of specific pathogens, were randomly divided into four groups: a normal control group (ZC), a standing group (ZL), a standing combined with lard group (ZLZ), and a standing combined with internal and external wet conditions group (ZLZS). The mice in the ZL, ZLZ, and ZLZS groups were subjected to 4 hours of daily standing in a custom-designed multiplatform water environment. Starting on day 8, mice in the ZLZ and ZLZS groups were gavaged with lard (0.4 mL per session, twice daily) for 7 consecutive days, while those in the ZLZS group were additionally exposed to a wet litter environment (50 g/100 mL). The ZC and ZL groups received equal volumes of sterile water via gavage. The microbiota in the small intestine, as well as serum levels of cAMP, cGMP, VIP, Gas, and D-xylose, were analyzed. Results: Compared with the ZLZ group, the ZLZS group showed significantly lower serum levels of cAMP/cGMP (p <0.01) and Gas (p <0.01). D-xylose levels were lower in the ZL, ZLZ, and ZLZS groups compared to the ZC group, while VIP levels were significantly higher in the ZL and ZLZS groups (p <0.01). Moverover, Corynebacterium , Empedobacter , and Pseudochrobactrum were identified as characteristic bacterial genera in the ZLZS group. The mechanism by which the small intestinal microbiota induces diarrhea was linked to the biosynthesis of secondary bile acids. Conclusion: A multiplatform water environment combined with lard gavage can effectively induce diarrhea, and the addition of an external wet environment exacerbates this condition by affecting small intestinal contents microbiota and other functions. [ABSTRACT FROM AUTHOR]

Liver fibrosis (LF) is a common sequela to diverse chronic liver injuries, leading to rising rates of cirrhosis and hepatocellular carcinoma (HCC). As the medicinal and edible homologous material, traditional teas have exhibited promising applications in the clinical management of liver fibrosis. Here, we generated a liver fibrosis mouse model to explore the potent therapeutic ability of Ampelopsis grossedentata (AG) tea on this condition by multi-omics analysis. The biochemistry results pointed towards mitigated increases of ALT, AST, TBIL, and ALP triggered by BDL in the AG-treated group. Examination using H&E and Sirius Red staining revealed severe liver injuries, inflammation infiltration, amplified fibrosed regions, and the creation of bile ducts, all of which were fallout from BDL. Immunohistochemistry findings also implicated a noteworthy upregulation of the HSC activation marker α-smooth muscle actin (α-SMA) and the fibrosis marker collagen I in the BDL group. However, these symptoms demonstrated a significant improvement in the group treated with 100 mg/kg AG. Findings from the Western Blot test corroborated the prominent elevation of TNF-α, col1a1, α-SMA, and TGF-β, instigated by BDL, while AG treatment meaningfully modulated these proteins. Furthermore, our study underscored the potential involvement of several microbiota, such as Ruminococcaceae UCG-014, Eubacterium Ruminantium, Ruminococcus 1, Christensenellaceae R-7, Acetatifactor, Dubosiella, Parasutterella, Faecalibaculum, and Defluviitaleaceae UCG-011, in the progression of liver fibrosis and the therapeutic efficacy of AG. This investigation shows that during the process of AG ameliorating BDL-induced liver fibrosis, bile acid derivatives such as CDCA, TCDCA, 3-DHC, UCA, DCA, among others, play significant roles. In this study, we identified that several non-bile acid metabolites, such as Deltarasin, Thr-Ile-Arg, etc., are entailed in the process of AG improving liver fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Deceleration of disease progression and re-establishment of microbial balance in the gut is often achieved by application of lactobacilli strains. Their beneficial effects are associated with probiotic properties, which may be accompanied by immunomodulatory action at mucosal surfaces. Methods: To single out such strains, we screened almost three hundred lactobacilli isolates from eight genera and various food sources for acid and bile salt tolerance, adhesion to mucin as well as hemolytic activity and antibiotic susceptibility. Moreover, the immunomodulatory effects of cell-free supernatant (CFS) fractions of five lactobacilli strains were assessed using an in vitro cell line model. Results and discussion: By our rationalized selection approach, we identified thirty-five strains with probiotic potential and biosafety features. Additionally, we showed that CFS from the Lactiplantibacillus L_4 strain downregulates proinflammatory cytokines IL-8 and IL-1β. In contrast, IL-8 expression was found to increase after treatment with CFSs of Lactiplantibacillus L_2 and L_5 and IL-1β was upregulated by CFSs of Lactiplantibacillus L_1 and Lactiplantibacillus L_3. Overall, our result delineate a rational approach of selecting lactobacilli strains for probiotic development to support the gut microbiota equilibrium and reinforce the host immune system. [ABSTRACT FROM AUTHOR]

Objective: NOTES gallbladder‐preserving surgery (N‐GPS) has been heralded as a new paradigm shift in minimally invasive surgery for chronic cholecystitis patients. The objective of this research was to evaluate the impact of N‐GPS on the intestinal microbiota of patients. Methods: The study selected patients with benign gallbladder disease (BG group) within 1 week preoperative (BG_DPR stage) and followed up over 1 year postoperative (BG_YPO stage) and selected healthy controls (HC group) whose sex, age, and BMI index matched with patients at BG_YPO stage, too. Accordingly, stool samples from healthy controls and two stages of patients with benign gallbladder disease were collected; among them, the selected samples were sent for 16S rDNA sequencing with Illumina MiSeq platform, and then, the combined samples were sent for short‐chain fatty acid (SCFA) analysis with GC‐MS platform. Results: The result of alpha diversity of Shannon index showed that the difference among the two stages of BG group and HC group wasn't statistically significant, while the result of beta diversity based on the weighted UniFrac distance suggested that the structure of intestinal microbiota of BG group at YPO stage was closer to HC group. LEfSe analysis suggested that BG_YPO stage enriched genus, such as Enterocloster and Hungatella_A_128155, which improved bile acid metabolism. Compared with BG_DPR stage, BG_YPO stage and HC group enriched Faecalibacterium and Roseburia, but depleted Streptococcus, while fecal SCFA concentrations increased. Conclusion: Patients with benign gallbladder disease and chronic cholecystitis after N‐GPS treatment for over 1 year improved gut microbial community structure. With the improving bile acid metabolism, SCFA‐producing bacteria increased and pathobionts decreased, which helped the intestinal microbiota structure of BG group at YPO stage restore and close to HC group. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR1900028267. [ABSTRACT FROM AUTHOR]

The dysfunction of gut microbiome and bile acid metabolism might cause the incidence and relapse of ulcerative colitis (UC). Thus, natural products have been considered effective for UC through the regulation of gut microbiome and bile acid. In this study, we evaluated the regulatory effect of berberine on gut microbiome and bile acid metabolism in UC. Results showed that the relative abundances of beneficial bacteria showed a decreasing trend in the UC model, and the taurine conjugated bile acids increased from the liver tissue to the colon tissue. Berberine inhibited the colonization of harmful bacteria and promoted the primary bile acid metabolism. Moreover, we used multi-omics technology (metagenomics, metabolomics, and transcriptomics technology) to reveal that berberine restored the intestinal barrier function through bile acid/S1PR2/RhoA/ROCK pathway. The result of transmission electron microscopy directly showed that the damaged intestinal mucosal barrier was repaired through the berberine treatment. This study revealed the treatment influence on UC through multi-omics technology in vitro and in vivo models, which provides references for explaining the mechanism of berberine on UC. [ABSTRACT FROM AUTHOR]

Background: Microbial-derived secondary bile acids (SBAs) are reabsorbed and sensed via host receptors modulating cellular inflammation and fibrosis. Feline chronic kidney disease (CKD) occurs with progressive renal inflammation and fibrosis, mirroring the disease pathophysiology of human CKD patients. Methods: Prospective cross-sectional study compared healthy cats (n = 6) with CKD (IRIS Stage 2 n = 17, Stage 3 or 4 n = 11). Single timepoint fecal samples from all cats underwent targeted bile acid metabolomics. 16S rRNA gene amplicon sequencing using DADA2 with SILVA taxonomy characterized the fecal microbiota. Results: CKD cats had significantly reduced fecal concentrations (median 12.8 ng/mg, Mann–Whitney p = 0.0127) of the SBA ursodeoxycholic acid (UDCA) compared to healthy cats (median 39.4 ng/mg). Bile acid dysmetabolism characterized by <50% SBAs was present in 8/28 CKD and 0/6 healthy cats. Beta diversity significantly differed between cats with <50% SBAs and > 50% SBAs (PERMANOVA p < 0.0001). Twenty-six amplicon sequence variants (ASVs) with >97% nucleotide identity to Peptacetobacter hiranonis were identified. P. hiranonis combined relative abundance was significantly reduced (median 2.1%) in CKD cats with <50% SBAs compared to CKD cats with >50% SBAs (median 13.9%, adjusted p = 0.0002) and healthy cats with >50% SBAs (median 15.5%, adjusted p = 0.0112). P. hiranonis combined relative abundance was significantly positively correlated with the SBAs deoxycholic acid (Spearman r = 0.5218, adjusted p = 0.0407) and lithocholic acid (Spearman r = 0.5615, adjusted p = 0.0156). Three Oscillospirales ASVs and a Roseburia ASV were also identified as significantly correlated with fecal SBAs. Clinical and translational importance: The gut-kidney axis mediated through microbial-derived SBAs appears relevant to the spontaneous animal CKD model of domestic cats. This includes reduced fecal concentrations of the microbial-derived SBA UDCA, known to regulate inflammation and fibrosis and be reno-protective. Microbes correlated with fecal SBAs include bai operon containing P. hiranonis , as well as members of Oscillospirales , which also harbor a functional bai operon. Ultimately, CKD cats represent a translational opportunity to study the role of SBAs in the gut-kidney axis, including the potential to identify novel microbial-directed therapeutics to mitigate CKD pathogenesis in veterinary patients and humans alike. [ABSTRACT FROM AUTHOR]

The article focuses on a case of a 1.5-year-old Thoroughbred colt with persistently elevated liver enzymes, bile acids, icterus, and weight loss, which ultimately led to a diagnosis of hepatoblastoma. Topics include clinical signs and diagnostic challenges in young horses with liver disease, the role of liver enzyme elevations in diagnosis, and the poor prognosis for horses diagnosed with hepatoblastoma due to limited treatment options.

Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE‐mediated food allergy are unknown. Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT. Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes. Results: Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10−20) and linoleic acid derivatives (q = 3.8 × 10−5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10−8), eicosanoids (q = 7.9 × 10−7), and histidine pathways (q =.015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p =.0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p =.01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p =.0015) were higher in SU. Conclusions: We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T‐cell subsets, suggesting potential mechanisms of tolerance in immunotherapy. [ABSTRACT FROM AUTHOR]

Objective • To provide a theoretical basis for intestinal intervention in the treatment of coronary heart disease. Methods• Summarizing the mechanism of trimethylamine oxide (TMAO) inducing coronary heart disease and discussing the target of clinical intervention including TMAO generation, metabolism, and other links. The authors also clarified the potential clinical value of TMAO as a predictor of cardiovascular disease． Results • The intestinal microbiota metabolite TMAO is closely related to the occurrence and development of coronary heart disease. TMAO can induce the development of coronary heart disease by promoting endothelial cell dysfunction, promoting foam cell formation, affecting cholesterol and bile acid metabolism, and promoting platelet activation and thrombosis. Diet, physical exercise, and other ways can reshape intestinal flora, inhibit TMAO generation, and help to prevent and cure coronary heart disease. In addition, TMAO has important clinical value in predicting risk stratification and evaluating the prognosis of coronary heart disease. Conclusion• TMAO can induce and assist in the development of coronary heart disease by promoting endothelial cell dysfunction, foam cell formation, and other mechanisms. At present, diet and physical exercise can reduce the production of TMAO to a certain extent, to prevent the occurrence and development of coronary heart disease. Furthermore, TMAO is a promising predictive marker for risk stratification and evaluating the prognosis of coronary heart disease. TMAO can not only directly induce coronary heart disease by promoting endothelial cell dysfunction, foam cell formation and other mechanisms, but also promote the occurrence and development of coronary heart disease by affecting the risk factors related to coronary heart disease (such as hypertension and diabetes). It has been confirmed that diet and physical exercise can reduce the production of TMAO to a certain extent and prevent the occurrence and development of coronary heart disease. In addition, TMAO is a valuable indicator for assessing risk stratification and prognosis of coronary heart disease. [ABSTRACT FROM AUTHOR]

Background/Objectives: Growing evidence suggests that cholecystectomy is associated with adverse health outcomes, including the development of metabolic diseases. However, data on the association between cholecystectomy and kidney disease are limited. The present study aimed to investigate the association between cholecystectomy and chronic kidney disease (CKD) using a nationwide longitudinal cohort. Methods: Participants aged ≥20 years with cholecystectomy between 2010 and 2014 (n = 116,748) and age- and sex-matched control participants without cholecystectomy (n = 116,748) were analyzed using the Korea National Health Insurance Service data. The adjusted hazard ratios (aHRs) were calculated for incident CKD in the cholecystectomy group compared with the nonoperative controls. Results: A total of 233,496 participants were included (mean age, 54.7 ± 12.7 years; 52.6% men). During the mean follow-up period of 4.8 ± 1.7 years, 6450 patients (5.5%) were newly diagnosed with CKD in the cholecystectomy group. Cholecystectomy was an independent risk factor for the development of CKD after adjustment for confounders, including age, sex, income, health behaviors, and comorbidities. The risk of CKD was 21% higher in the cholecystectomy group compared to the non-cholecystectomy group (aHR, 1.21; 95% CI, 1.17–1.26). The increased risk of CKD in the cholecystectomy group was consistently significant when a stratified analysis by age, sex, and presence or absence of comorbidities was conducted. Conclusions: Cholecystectomy was independently associated with an increased risk of developing CKD in a nationwide population-based study. Therefore, careful and long-term monitoring of the risk of CKD after cholecystectomy is necessary. [ABSTRACT FROM AUTHOR]

Dietary lipid absorption is facilitated by bile acids. In the Zucker rat (ZR) model of obesity, bile acid absorption, mediated by the apical sodium bile acid transporter (ASBT), was increased in villus cells from the distal ileum. However, whether ASBT may be de novo expressed more proximally in the small intestine during obesity to facilitate additional bile acid absorption is not known. For this, starting from the end of the ileum to the mid jejunum, caudal-orally, five intestinal segments of equal length (S1–S5) were separated from lean and obese ZRs (LZR and OZR). Intestinal mucosa obtained from these segments were used for total RNA extraction, RT-qPCR and 3H-TCA uptake. The results showed that bile acid absorption along with the mRNA expression of ASBT and FXR progressively decreased caudal-orally in both LZRs and OZRs but was significantly higher in all small intestinal segments in OZRs. The expression of GATA4 was absent in the distal ileum (S1) in both LZRs and OZRs, but steadily increased along the proximal length in both. However, this steady increase was significantly reduced in the comparative obese proximal intestinal segments S2, S3, S4 and S5. The expressions of bile acid-activated G-protein-coupled bile acid receptor TGR5 and S1PR2 were unaltered in segments S1–S4 but were significantly increased in OZR S5. The paradigm changing observation of this study is that ASBT is expressed more proximally in the small intestine in obesity. This likely increases overall bile acid absorption and thereby lipid absorption in the proximal small intestine in obesity. [ABSTRACT FROM AUTHOR]

The transition from pregnancy to lactation is critical in dairy cows. Among others, dairy cows experience a metabolic stress due to a large change in glucose and lipid metabolism. Recent studies revealed that bile acids (BA), other than being involved in both the emulsification and solubilization of fats during intestinal absorption, can also affect the metabolism of glucose and lipids, both directly or indirectly by affecting the gut microbiota. Thus, we used untargeted and targeted metabolomics and 16S rRNA gene sequencing approaches to investigate the concentration of plasma metabolites and BA, the composition of the rectum microbial community, and assess their interaction in transition dairy cows. In Experiment 1, we investigated BA and other blood parameters and gut microbiota in dairy cows without clinical diseases during the transition period, which can be seen as well adapted to the challenge of changed glucose and lipid metabolism. As expected, we detected an increased plasma concentrations of BHB and nonesterified fatty acids (NEFA) but decreased concentrations of glucose, cholesterol, and triglycerides (TG). Untargeted metabolomic analysis of the plasma revealed primary BA biosynthesis was one of the affected pathways, and was consistent with the increased concentration of BA in the plasma. A correlation approach revealed a complex association between BA and microbiota with the host plasma concentration of glucose and lipid metabolites. Among BA, chenodeoxycholic acid derivates such as glycolithocholic acid, taurolithocholic acid, lithocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites (such as glucose, TG, and NEFA). In Experiment 2, we investigated early postpartum dairy cows with or without hyperketonemia (HPK). As expected, HPK cows had increased concentration of NEFA and decreased concentrations of glucose and triglycerides. The untargeted metabolomic analysis of the plasma revealed that primary BA biosynthesis was also one of the affected pathways. Even though the BA concentration was similar among the 2 groups, the profiles of taurine-conjugated BA changed significantly. A correlation analysis also revealed an association between BA and microbiota with the concentration in plasma of glucose and lipid metabolites (such as BHB). Among BA, cholic acid and its derivates such as taurocholic acid, tauro α-muricholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites. Our results indicated an association between BA, intestinal microbe, and glucose and lipid metabolism in transition dairy cows. These findings provide new insight into the adaptation mechanisms of dairy cows during the transition period. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Aim: Echocardiography is necessary for portopulmonary hypertension diagnosis, and identifying patients with cirrhosis who require it is challenging. In this study, we aimed to investigate the utility of the total bile acid (TBA) levels as a screening tool for identifying patients with decompensated cirrhosis who should undergo echocardiography for portopulmonary hypertension diagnosis. Methods: We evaluated 135 patients with decompensated cirrhosis who underwent liver transplantation. Subsequently, factors contributing to tricuspid regurgitation pressure gradient (TRPG) elevation (≥30 mmHg) were analyzed using preoperative data, including the TBA levels. Results: The median age of patients was 58 years (61 women), and 45 and 90 patients had Child–Turcotte–Pugh grades of B and C, respectively. The median TRPG level was 21 mmHg, and 17 patients (12.6%) showed TRPG elevation. Multiple logistic regression analysis revealed that elevated TBA (odds ratio 4.322; p = 0.013) and main pulmonary artery diameter ≥33 mm (odds ratio 4.333; p = 0.016) were significantly associated with TRPG elevation. The TBA cut‐off value (167.7 μmol/L) showed a high diagnostic performance, with 70.6% sensitivity and 64.4% specificity. Ursodeoxycholic acid (UDCA) administration increased the TBA levels dose‐dependently. Analysis stratified by UDCA use revealed that in patients not taking UDCA (n = 59), elevated TBA levels and younger age significantly contributed to TRPG elevation. However, in those taking UDCA (n = 76), this contribution disappeared, suggesting that UDCA consumption reduced TBA levels' efficiency in diagnosing TRPG elevation. Conclusions: The TBA levels may be a potential screening tool for TRPG elevation; however, caution is warranted when interpreting cases treated with UDCA. [ABSTRACT FROM AUTHOR]

Background: Colonic transit (CT) measured by validated scintigraphy using 111In‐labeled activated charcoal particles is summarized using geometric center (GC) of isotopic distribution in four colonic regions and stool at 24 and 48 h. Diagnosis of rapid CT is currently based on GC24 ≥4.4 in females and >4.7 in males, which lack sensitivity. Our aim was to evaluate, in patients with chronic diarrhea with normal CT by GC24 and GC48, the diagnostic utility of CT change (∆GC) relative to sex‐matched normal values. Methods: We evaluated two adult patient cohorts: 701 clinical patients (1994–2023) with chronic diarrhea and 76 research participants with irritable bowel syndrome with diarrhea (N = 63) or bile acid diarrhea (BAD, N = 13). Results of ∆GC were compared to 220 healthy controls' 95th percentiles (%ile) (≥2.0 females and ≥2.2 males). In the research cohort, we also analyzed (Spearman correlation) colonic ∆GC with ascending colon emptying T1/2 (AC T1/2), average stool frequency and consistency based on a daily diary, total fecal bile acid (BA) concentration, and % primary BA in a single stool sample. Key Results: Among 701 clinical patients with normal GC24, 160 (22.3%) had rapid CT based on ∆GC 95th %ile in health. Among 76 research participants, an additional 20.6% IBS‐D and 23% BAD had rapid CT ∆GC. Younger age and absence of diabetes mellitus were predictive of rapid ∆GC. ∆GC significantly correlated with AC T1/2 and with fecal BA. Conclusions & Inferences: ∆GC identified an additional 21%–23% patients with rapid colonic transit among patients with diarrhea and normal GC24. [ABSTRACT FROM AUTHOR]

Background: Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut‐brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events. Purpose: The aims of this review are to evaluate the evidence for efficacy of second‐ and third‐line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review. [ABSTRACT FROM AUTHOR]

• Three different MSCs have varied therapeutic effects on AD model mice. • The gut microbiota dysbiosis of AD mice could be partially recovered after MSC treatment, antibiotic diminished the therapeutic impacts of MSCs. • MSCs treatment affected the bile acids related microbiota and metabolites. • Both MSCs and bile acids mediate the therapeutic outcomes in AD mice through MGBA. The intricacy and multifaceted nature of Alzheimer's disease (AD) necessitate therapies that target multiple aspects of the disease. Mesenchymal stromal cells (MSCs) emerge as potential agents to mitigate AD symptoms; however, whether their therapeutic efficacy involves modulation of gut microbiota and the microbiome-gut-brain axis (MGBA) remains unexplored. In this study, we evaluated the effects of three distinct MSCs types—derived from the umbilical cord (UCMSC), dental pulp (SHED), and adipose tissue (ADSC)—in an APP/PS1 mouse model of AD. In comparison to saline control, MSCs administration resulted in a significant reduction of behavioral disturbances, amyloid plaques, and phosphorylated tau in the hippocampus and frontal cortex, accompanied by an increase in neuronal count and Nissl body density across AD-afflicted brain regions. Through 16S rRNA gene sequencing, we identified partial restoration of gut microbial balance in AD mice post-MSCs treatment, evidenced by the elevation of neuroprotective Akkermansia and reduction of the AD-associated Sphingomonas. To examine whether gut microbiota involved in MSCs efficacy in treating AD, SHED with better anti-inflammatory and gut microbiota recovery effects among three MSCs, and another AD model 5 × FAD mice with earlier and more pathological proteins in brain than APP/PS1, were selected for further studies. Antibiotic-mediated gut microbial inactivation attenuated MSCs efficacy in 5 × FAD mice, implicating the involvement of gut microbiota in the therapeutic mechanism. Functional analysis of altered gut microbiota and targeted bile acid metabolism profiling revealed a significant enhancement in bile acid variety following MSCs therapy. A chief bile acid constituent, taurocholic acid (TCA), was orally administered to AD mice and similarly abated AD symptoms. Nonetheless, the disruption of intestinal neuronal integrity with enterotoxin abrogated the ameliorative impact of both MSCs and TCA treatments. Collectively, our findings substantiate that MSCs confer therapeutic benefits in AD within a paradigm that primarily involves regulation of gut microbiota and their metabolites through the MGBA. [ABSTRACT FROM AUTHOR]

Early allograft dysfunction (EAD) is a frequent phenomenon, leading to increased graft loss and higher mortality after liver transplantation (LT). Despite significant efforts for early diagnosis of EAD, there is no existing approach that can predict EAD on the first post‐operative day. The aim is to define a metabolite‐based biomarker on the first day after LT complicated with EAD. Ten patients diagnosed with EAD and 26 non‐EAD are recruited for the study. A HPLC‐MS/MS is used to determine 14 amino acids and 15 bile acids serum concentration. Comparative analyses are conducted between EAD and non‐EAD groups. Arginine is identified as the most significant metabolite distinguishing the EAD and non‐EAD groups, and therefore, is identified as a potential biomarker of EAD. The optimal cut‐off value for arginine is 52.09 µmol L−1, with an AUROC of 0.804 (95% confidence interval: 0.638–0.917, p < 0.001), yielding a sensitivity of 100%, specificity of 53.8%, and Youden index of 0.54, NPVof 100%, and PPV of 45.45%. In summary, the study indicated that targeted metabolomics analysis would be a promising strategy for discovering novel biomarkers to predict EAD. The identified arginine may be helpful in developing an objective diagnostic method for EAD. [ABSTRACT FROM AUTHOR]

The tolerance of Saccharomyces cerevisiae to high concentrations of bile acids is intricately linked to its potential as a probiotic. While the survival of yeast under high concentrations of bile acids has been demonstrated, the specific mechanisms of tolerance remain inadequately elucidated. This study aims to elucidate the tolerance mechanisms of S. cerevisiae CEN.PK2-1C under conditions of elevated bile acid concentrations. Through growth curve analyses and scanning electron microscopy (SEM), we examined the impact of high bile acid concentrations on yeast growth and cellular morphology. Additionally, transcriptomic sequencing and molecular docking analyses were employed to explore differentially expressed genes under high bile acid conditions, with particular emphasis on ATP-binding cassette (ABC) transporters and steroid hormone biosynthesis. Our findings indicate that high concentrations of bile acids induce significant alterations in the sterol synthesis pathway and transporter protein expression in S. cerevisiae. These alterations primarily function to regulate sterol synthesis pathways to maintain cellular structure and sustain growth, while enhanced expression of transport proteins improves tolerance to elevated bile acid levels. This study elucidates the tolerance mechanisms of S. cerevisiae under high bile acid conditions and provides a theoretical foundation for optimizing fermentation processes and process control. [ABSTRACT FROM AUTHOR]

(1) Background: This study investigated the impact of in vitro adaptations to acid and bile stress on the cholesterol-lowering activity of the probiotic Lactobacillus kefir M20. (2) Methods: Lactobacillus kefir M20 was extracted from fermented dairy products in Xinjiang, China, and isolated using MRS medium. The lactic acid bacteria were cultured for stress resistance to acid and bile salts and then gavaged into mice for animal experiments. (3) Results: The adaptation to bile stress treatment resulted in a notable enhancement of the cholesterol-lowering capacity of Lactobacillus kefir M20, with reductions of 16.5% and 33.1% in total and non-HDL cholesterol, respectively, compared to the untreated strain. Furthermore, the daily fecal total bile acid excretion was 9.2, 5.4 and 5.0 times higher in the M20-BSA group compared to the HC, M20 and M20-ASA groups, respectively. (4) Conclusions: This study suggests that targeted probiotics have the potential for application in the next generation of functional foods and probiotic formulations aimed at combating hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Purpose We aimed to explore the causal relationship between human serum metabolites and angina pectoris. Methods This study used two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and angina pectoris. The analytical methods employed to reduce study bias included inverse variance weighted, MR-Egger, and weighted median method. A comprehensive sensitivity analysis was performed using the leave-one-out method, while instrumental variable pleiotropy was tested with MR-Pleiotropy RESidual Sum and Outlier. Metabolic pathways of angina-associated metabolites were analysed on the MetaboAnalyst metabolomics analysis tool platform. Results In this study, 42 serum metabolites were found to be strongly associated with angina pectoris. They mainly belonged to seven groups: amino acids, carbohydrates, cofactors and vitamins, lipids, nucleotides, unknown metabolites, and exogenous substances. Pipecolate posed the highest risk for the development of angina pectoris among the 42 serum metabolites. The main metabolic pathways associated with angina pectoris were glycine, serine, threonine metabolism, primary bile acid biosynthesis, and caffeine metabolism. Conclusion We identified 25 high-risk and 17 protective human serum metabolites associated with angina pectoris. Their associated major metabolic pathways were also determined. The serum metabolite pipecolate was significantly and positively correlated with the risk of angina pectoris. This finding may serve as a valuable reference for testing serum markers associated with angina pectoris. Key message What is already known on this topic Recently, some progress has been made in screening biomarkers of angina serum metabolism. However, no studies explored the link between serum metabolites and angina pectoris using MR analysis. What this study adds In this study, Mendelian randomization analysis was conducted for the first time on the association between human serum metabolites and angina pectoris, and 42 serum metabolites were found to be strongly associated with angina pectoris. How this study might affect research, practice, or policy This study might assist in the clinical diagnosis and treatment of angina pectoris and advance coronary heart disease prevention and treatment. [ABSTRACT FROM AUTHOR]

Background:The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism. Methods: 16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues. Results: The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway. Conclusion: Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. Methods: This case–control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24‐segment spherical indices (SIs) were measured and compared between groups. Results: The routine fetal cardiac parameters, global and right‐ventricular SIs did not differ between the ICP and control groups. The left‐ventricular apical (segments 16‐24) SIs were lower in the ICP group than in the control group (P <.05), with no significant difference in the other left‐ventricular segments. Conclusions: Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty‐four‐segment SIs can be used to effectively evaluate these changes. [ABSTRACT FROM AUTHOR]

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Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT‐induced cholestasis at 8–16 h. The distinguishing features of ANIT‐induced liver injury were as follows: T‐BAs exceeding G‐BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T‐BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT‐induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine‐conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained. Maintaining bile acid balance is important for liver health, with cholestatic liver injury often linked to bile acid profile disruptions. We investigated these disturbances and their correlation with liver damage post‐ANIT treatment. The alteration of bile acid profiles in plasma and liver occurred at 8–16 h before injury, persisting for up to 96 h. Certain bile acids emerged as early markers for diagnosing cholestasis. TCA in plasma, especially, showed high sensitivity to ANIT‐induced liver damage, exacerbating its progression. [ABSTRACT FROM AUTHOR]

Oleanolic acid (OA) is a naturally occurring pentacyclic triterpene compound that has been reported to cause cholestatic liver injury. However, the regulation and pathogenic role of bile acids in OA‐induced development of cholestatic liver injury remains largely unclear. Farnesoid X receptor (FXR) is a metabolic nuclear receptor that plays an important role in bile acid homeostasis in the liver by regulating efflux transporters bile salt export pump (BSEP) and multidrug resistance‐associated protein 2 (MRP2). The aim of this study was to investigate the effect of OA on hepatocyte tight junction function and determine the role of FXR, BSEP, and MRP2 in the mechanism of impairment of transport of bile acids induced by OA. Both in vivo and in vitro models were used to characterize the OA‐induced liver injury. The liquid chromatography–tandem mass spectrometry (LC‐MS) was employed to characterize the efflux function of the transporters, and the results showed that OA caused a blockage of bile acids efflux. OA treatment resulted in decreased expression levels of the tight junction proteins zonula occludens‐1 and occludin. Immunofluorescence results showed that OA treatment significantly reduced the number of bile ducts and the immunofluorescence intensity. Pretreatment with agonists of FXR and MRP2, respectively, in animal experiments attenuated OA‐induced liver injury, while pretreatment with inhibitors of BSEP and MRP2 further aggravated OA‐induced liver injury. These results suggest that OA inhibits FXR‐mediated BSEP and MRP2, leading to impaired bile acid efflux and disruption of tight junctions between liver cells, resulting in liver damage. Oleanolic acid (OA) is a naturally occurring pentacyclic triterpene compound that has been reported to cause cholestatic liver injury. In this study, OA inhibits FXR‐mediated BSEP and MRP2, leading to impaired bile acid efflux and disruption of tight junctions between liver cells, resulting in liver damage. Activation of FXR and MRP2 mitigated OA‐induced liver injury, while inhibition of BSEP and MRP2 further aggravated OA‐induced liver injury. [ABSTRACT FROM AUTHOR]

In recent years, with the rapid development of omics technologies, researchers have shown that interactions between the intestinal flora and bile acids are closely related to the progression of diabetic kidney disease (DKD). By regulating bile acid metabolism and receptor expression, the intestinal flora affects host metabolism, impacts the immune system, and exacerbates kidney injury in DKD patients. To explore interactions among the gut flora, bile acids and DKD, as well as the related mechanisms, in depth, in this paper, we review the existing literature on correlations among the gut flora, bile acids and DKD. This review also summarizes the efficacy of bile acids and their receptors as well as traditional Chinese medicines in the treatment of DKD and highlights the unique advantages of bile acid receptors in DKD treatment. This paper is expected to reveal a new and important potential strategy for the clinical treatment of DKD. [ABSTRACT FROM AUTHOR]

Molecular biomarkers preserved in lake sediments are increasingly used to develop records of past organism occurrence. When linked with traditional paleoecological methods, analysis of molecular biomarkers can yield new insights into the roles of herbivores and other animals in long-term ecosystem dynamics. We sought to determine whether fecal steroids in lake sediments could be used to reconstruct past ungulate use and dominant taxa in a small catchment in northern Yellowstone National Park. To do so, we characterized the fecal steroid profiles of a selection of North American ungulates historically present in the Yellowstone region (bison, elk, moose, mule deer, and pronghorn) and compared them with those of sediments from a small lake in the Yellowstone Northern Range. Analysis of a set of fecal steroids from herbivore dung (Δ5-sterols, 5α-stanols, 5β-stanols, epi5β-stanols, stanones, and bile acids) differentiated moose, pronghorn, and mule deer, whereas bison and elk were partially differentiated. Our results show that bison and/or elk were the primary ungulates in the watershed over the past c. 2300 years. Fecal steroid influxes reached historically unprecedented levels during the early and middle 20th century, possibly indicating high local use by ungulates. Comparison of fecal steroid influxes with pollen and diatom data suggests that elevated ungulate presence may have contributed to decreased forage taxa (Poaceae, Artemisia, and Salix), relative to long-term averages, and possibly increased lake production. Our results reflect past change within a single watershed, and extending this approach to a network of sites could provide much-needed information on past herbivore communities, use, and environmental influences in Yellowstone National Park and elsewhere. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma is a highly heterogeneous tumor with bile acid metabolism involving in its development. The aim of this study was to characterize bile acid metabolism and identify specific subtypes to better stratify cholangiocarcinoma patients for individualized treatment and prognostic assessment. Methods: A total of 30 bile acids were quantified using the ultra-performance liquid chromatography tandem mass spectrometry. Using Consensus clustering, the molecular subtypes related to bile acid metabolism were identified. The prognosis, clinicopathologic characteristics, immune landscape, and therapeutic response were compared between these subtypes. The single-cell RNA sequencing (scRNA-seq) analysis and preliminary cell experiment were also conducted to verify our findings. Results: The altered bile acid profile and genetic variation of bile acid metabolism-related genes in cholangiocarcinoma were demonstrated. The cholangiocarcinoma was categorized into bile acid metabolism-active and -inactive subtypes with different prognoses, clinicopathologic characteristics, tumor microenvironments (TME) and therapeutic responses. This categorization was reproducible and predictable. Specifically, the bile acid metabolism-active subtype showed a poor prognosis with an immunosuppressive microenvironment and an inactive response to immunotherapy, while the bile acid metabolism-inactive subtype showed the opposite characteristics. Moreover, the scRNA-seq revealed that immunotherapy altered bile acid metabolism in TME of cholangiocarcinoma. Finally, a prognostic signature related to bile acid metabolism was developed, which exhibited strong power for prognostic assessment of cholangiocarcinoma. Consistently, these results were verified by immunohistochemistry, cell proliferation, migration, and apoptosis assays. Conclusion: In conclusion, a novel cholangiocarcinoma classification based on bile acid metabolism was established. This classification was significant for the estimation of TME and prognosis. [ABSTRACT FROM AUTHOR]

Background: Low birth weight (LBW; <2,500 g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings. Methods: This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 weeks were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine. Results: No differences in ß-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 weeks was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers p < 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance. Conclusion: Collectively, the findings indicate that alterations in the maternal microbiome and metabolome were associated with LBW. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight. [ABSTRACT FROM AUTHOR]

Introduction: Canine protein-losing enteropathy (PLE) is a syndrome characterized by gastrointestinal loss of proteins. While fecal microbiome and metabolome perturbations have been reported in dogs with chronic enteropathy, they have not been widely studied in dogs with PLE. Therefore, the study aims were to investigate gut microbiome and targeted fecal metabolites in dogs with inflammatory PLE (iPLE) and evaluate whether treatment affects these changes at short-term follow-up. Methods: Thirty-eight dogs with PLE and histopathological evidence of gastrointestinal inflammation and 47 healthy dogs were enrolled. Fecal samples were collected before endoscopy (T0) and after one month of therapy (T1). Microbiome and metabolome alterations were investigated using qPCR assays (dysbiosis index, DI) and gas chromatography/mass spectrometry (long-chain fatty acids, sterols, unconjugated bile acids), respectively. Results: Median (min-max) DI of iPLE dogs was 0.4 (-5.9 to 7.7) and was significantly higher (p < 0.0001) than median DI in healthy dogs [-2.0 (-6.0 to 5.3)]. No significant associations were found between DI and selected clinicopathological variables. DI did not significantly differ between T0 and T1. In iPLE dogs, at T0, myristic, palmitic, linoleic, oleic, cis-vaccenic, stearic, arachidonic, gondoic, docosanoic, erucic, and nervonic acids were significantly higher (p < 0.0001) than healthy dogs. In iPLE dogs, oleic acid (p = 0.044), stearic acid (p = 0.013), erucic acid (p = 0.018) and nervonic acid (p = 0.002) were significantly decreased at T1. At T0, cholesterol and lathosterol (p < 0.0001) were significantly higher in iPLE dogs compared to healthy dogs, while total measured phytosterols were significantly lower (p = 0.001). No significant differences in total sterols, total phytosterols and total zoosterols content were found at T1, compared to T0. At T0, total primary bile acids and total secondary bile acids did not significantly differ between healthy control dogs and iPLE dogs. No significant differences in fecal bile acid content were found at T1. Discussion: Dysbiosis and lipid metabolism perturbations were observed in dogs with iPLE. Different therapeutic protocols lead to an improvement of some but not all metabolome perturbations at short-term follow-up. [ABSTRACT FROM AUTHOR]

Macaque restricts hepatitis B virus (HBV) infection because its receptor homologue, NTCP (mNTCP), cannot bind preS1 on viral surface. To reveal how mNTCP loses the viral receptor function, we here solve the cryo-electron microscopy structure of mNTCP. Superposing on the human NTCP (hNTCP)-preS1 complex structure shows that Arg158 of mNTCP causes steric clash to prevent preS1 from embedding onto the bile acid tunnel of NTCP. Cell-based mutation analysis confirms that only Gly158 permitted preS1 binding, in contrast to robust bile acid transport among mutations. As the second determinant, Asn86 on the extracellular surface of mNTCP shows less capacity to restrain preS1 from dynamic fluctuation than Lys86 of hNTCP, resulting in unstable preS1 binding. Additionally, presence of long-chain conjugated-bile acids in the tunnel induces steric hindrance with preS1 through their tailed-chain. This study presents structural basis in which multiple sites in mNTCP constitute a molecular barrier to strictly restrict HBV. Here the authors look at why macaque is non-susceptible to hepatitis B virus by focusing on the protein structure of the host receptor homolog. They show that macaque-derived host receptor homolog has multiple structural defects against virus binding. [ABSTRACT FROM AUTHOR]

Bile acid sequestrants (BASs) have often been used for bile acid diarrhea (BAD) but carry a high risk of adverse events. New generations of BASs show promising results; however, their efficacy remains unclear. This systematic review and meta‐analysis was conducted using PubMed, Cochrane, and Embase to assess randomized controlled trials (RCTs) published up to November 2023 to retrieve studies that measured the parameters before and after the administration of BASs. The outcomes assessed were cessation or improvement in diarrhea, fecal consistency, abdominal cramping, frequency of diarrhea, and adverse events. Risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled using a random‐effects model. Statistical analyses were conducted using RStudio version 4.1.2. The protocol was prospectively registered with PROSPERO (CRD42023445444). Seven RCTs with a total of 311 patients were included, of which 168 (54%) were randomized to BASs. Among BAS‐treated patients, 101 (60.1%) received colesevelam, 40 (23.8%) received chenodeoxycholate, 18 (10.7%) received cholestyramine, and 9 (5.3%) received colestid. BASs were associated with a significant improvement in the cessation of diarrhea (RR 3.27; 95% CI 2.08 to 5.15; P ≤  .05) and liquid stool to normal fecal consistency (RR 2.69; 95% CI 1.56 to 4.65; P ≤  .05), as well as an increase in abdominal cramps (RR 5.27; 95% CI 1.21 to 22.93; P ≤  .05). There were no differences in urgency, adverse events, or nausea between groups. These findings indicate that BASs are effective in the treatment of BAD, as indicated by the improvement or cessation of diarrhea episodes. [ABSTRACT FROM AUTHOR]

Long-standing chronic inflammation of the digestive tract leads to Inflammatory Bowel Diseases (IBD), comprising Crohn's Disease (CD) and Ulcerative colitis (UC). The persistent prevalence of these conditions in the gut is a predisposing factor for Colitis-Associated Cancer (CAC), one of the most common sub-types of Colorectal Cancer (CRC), emphasizing the role of inflammation in tumorigenesis. Therefore, targeted intervention of chronic intestinal inflammation is a potential strategy for preclusion and treatment of inflammation-driven malignancies. The association between bile acids (BA) and gut immune homeostasis has been explored in the recent past. However, the exact downstream mechanism by which secondary BA successfully regulating intestinal inflammation and inflammation-dependent CAC is unclear. Our study demonstrated that Ursodeoxycholic acid (UDCA), a secondary bile acid of host gut microbial origin, finetunes the dialogue between activated macrophages and intestinal epithelial cells, modulating inflammation-driven epithelial-mesenchymal transition (EMT), a hallmark of cancer. UDCA treatment and dependency on the TGR5/GPBAR1 receptor significantly upregulated the Suppressor of Cytokine Signaling 1 (SOCS1) expression, contributing to the regulation of pro-inflammatory cytokines in activated macrophages. In this study, we also noticed heightened expression of SOCS1 in UDCA-mitigated CAC in the AOM-DSS mouse model with reduced inflammatory gene expression. Overall, our observations highlight the possible utility of UDCA for inflammation-driven intestinal cancer. [ABSTRACT FROM AUTHOR]

Background: Metabolomics is an emerging field that quantifies numerous metabolites systematically aiming to determine the metabolites corresponding to each biological phenotype and then provide an analysis of the mechanisms involved. Bile acids (as an organic metabolites) are synthesized in the liver from cholesterol and could be used as indicator of hepatobiliary impairment. However, the role of these bile acids in the pathogenesis of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) is still unclear. Therefore, the current study aimed to use serum bile acid profiles potential diagnostic biomarkers for early detection of cholangiocarcinoma and differentiating it from hepatocellular carcinoma. Subjects and methods: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/ MS) analytical method was used for the measurement of bile acids in the serum of patients with hepatocellular carcinoma (n = 35), cholangiocarcinoma (n = 35), and control group (n = 35) to determine role as markers for differentiation between hepatocellular carcinoma and cholangiocarcinoma. Results: This study revealed that there was a significant increase in all 14 bile acids in both HCC and CCA compared to control. Also, there was significant increase in LCA, TCA, GDCA, and GCA in cholangiocarcinoma (CCA) compared to HCC with AUC 0.775, 0.825, 0.797, and 0.831 respectively with highest sensitivity and specificity for GCA (82% and 74%, respectively) for differentiation between the two types of cancers. Conclusion: Determination of the serum bile acids pattern using UPLC/MS/MS may help to differentiate between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) especially GCA which may be a good biomarker for differentiation between two types of liver cancers. [ABSTRACT FROM AUTHOR]

Background: Metabolic disorders have become one of the global medical problems. Due to the complexity of its pathogenesis, there is still no effective treatment. Bile acids (BAs) and gut microbiota (GM) have been proved to be closely related to host metabolism, which could be important targets for metabolic disorders. Zhi-Kang-Yin (ZKY) is a traditional Chinese medicine (TCM) formula developed by the research team according to theory of TCM and has been shown to improve metabolism in clinic. However, the underlying mechanisms are unclear. Aim of the study: This study aimed to investigate the potential mechanisms of the beneficial effect of ZKY on metabolism. Methods: High-fat diet (HFD)-fed mice were treated with and without ZKY. The glucose and lipid metabolism-related indexes were measured. BA profile, GM composition and hepatic transcriptome were then investigated to analyze the changes of BAs, GM, and hepatic gene expression. Moreover, the relationship between GM and BAs was identified with functional gene quantification and ex vivo fermentation experiment. Results: ZKY reduced weight gain and lipid levels in both liver and serum, attenuated hepatic steatosis and improved glucose tolerance in HFD-fed mice. BA profile detection showed that ZKY changed the composition of BAs and increased the proportion of unconjugated BAs and non-12-OH BAs. Hepatic transcriptomic analysis revealed fatty acid metabolism and BA biosynthesis related pathways were regulated. In addition, ZKY significantly changed the structure of GM and upregulated the gene copy number of bacterial bile salt hydrolase. Meanwhile, ZKY directly promoted the growth of Bifidobacterium, which is a well-known bile salt hydrolase-producing genus. The ex vivo co-culture experiment with gut microbiota and BAs demonstrated that the changes of BAs profile in ZKY group were mediated by ZKY-shifted GM, which led to increased expression of genes associated with fatty acid degradation in the liver. Conclusion: Our study indicated that the effect of ZKY on improving metabolism is associated with the modulation of GM-BAs axis, especially, by upregulating the abundance of bile salt hydrolase-expression bacteria and increasing the levels of unconjugated BAs. This study indicates that GM-BAs axis might be an important pathway for improving metabolic disorders by ZKY. [ABSTRACT FROM AUTHOR]

In this research, the dietary fibers (DFs) from ginseng residue were extracted by employing three different extraction methods (alkaline: AL, acidic: AC, enzymatic: EN). The extracted DFs were characterized in terms of their structural and functional properties. The results clearly showed that, regardless of the extraction methods, all DF samples exhibited representative infrared spectral features. The DF extracted by AC (citric acid) had more porous structures with a looser configuration, in conjunction with high apparent viscosity, whereas the DF extracted by EN (α-amylase and protease) exhibited higher thermal stability. Moreover, the monosaccharide composition of the DF samples was significantly influenced by the extraction method type. The DF from ginseng residue extracted by AC had the highest functional properties, such as water holding capacity (8.16 g/g), oil holding capacity (3.99 g/g), water swelling capacity (8.13 g/g), cholesterol-absorption capacity (12.85 mg/g), bile acid absorption capacity (91.51 mg/g), nitrite ion absorption capacity (124.38 ug/g at pH 2.0), glucose absorption capacity (52.67 mg/g at 150 mmol/L), as compared to those of DF extracted by the EN and AL (sodium hydroxide) methods. Hence, ginseng residue-derived DF extracted by the AC method may be potentially employed in the preparation of functional food ingredients. [ABSTRACT FROM AUTHOR]

Determining a novel etiology and mechanism of human cancer requires extraction of characteristic mutational signatures derived from chemical substances. This study explored the mutational signatures of N-nitroso bile acid conjugates using Salmonella strains. Exposing S. typhimurium TA1535 to N-nitroso-glycine/taurine bile acid conjugates induced a predominance of C:G to T:A transitions. Two mutational signatures, B1 and B2, were extracted. Signature B1 is associated with N-nitroso-glycine bile acid conjugates, while Signature B2 is linked to N-nitroso-taurine bile acid conjugates. Signature B1 revealed a strong transcribed strand bias with GCC and GCT contexts, and the mutation pattern of N-nitroso-glycine bile acid conjugates in YG7108, which lacks O6-methylguanine DNA methyltransferases, matched that of the wild-type strain TA1535, suggesting that O6-methyl-deoxyguanosine contributes to mutations in the relevant regions. COSMIC database-based similarity analysis revealed that Signature B1 closely resembled SBS42, which is associated with occupational cholangiocarcinoma caused by overexposure to 1,2-dichlolopropane (1,2-DCP) and/or dichloromethane (DCM). Moreover, the inflammatory response pathway was induced by 1,2-DCP exposure in a human cholangiocyte cell line, and iNOS expression was positive in occupational cholangiocarcinomas. These results suggest that 1,2-DCP triggers an inflammatory response in biliary epithelial cells by upregulating iNOS and N-nitroso-glycine bile acid conjugate production, resulting in cholangiocarcinoma via DNA adduct formation. [ABSTRACT FROM AUTHOR]

Understanding the systemic biochemistry of early pregnancy in the mare is essential for developing new diagnostics and identifying causes for pregnancy loss. This study aimed to elucidate the dynamic lipidomic changes occurring during the initial stages of equine pregnancy, with a specific focus on days 7 and 14 post-ovulation. By analysing and comparing the plasma lipid profiles of pregnant and non-pregnant mares, the objective of this study was to identify potential biomarkers for pregnancy and gain insights into the biochemical adaptations essential for supporting maternal recognition of pregnancy and early embryonic development. Employing discovery lipidomics, we analysed plasma samples from pregnant and non-pregnant mares on days 7 and 14 post-conception using the SCIEX ZenoTOF 7600 system. This high-resolution mass spectrometry approach enabled us to comprehensively profile and compare the lipidomes across these critical early gestational timepoints. Our analysis revealed significant lipidomic alterations between pregnant and non-pregnant mares and between days 7 and 14 of pregnancy. Key findings include the upregulation of bile acids, sphingomyelins, phosphatidylinositols, and triglycerides in pregnant mares. These changes suggest enhanced lipid synthesis and mobilization, likely associated with the embryo's nutritional requirements and the establishment of embryo–maternal interactions. There were significant differences in lipid metabolism between pregnant and non-pregnant mares, with a notable increase in the sterol lipid BA 24:1;O5 in pregnant mares as early as day 7 of gestation, suggesting it as a sensitive biomarker for early pregnancy detection. Notably, the transition from day 7 to day 14 in pregnant mares is characterized by a shift towards lipids indicative of membrane biosynthesis, signalling activity, and preparation for implantation. The study demonstrates the profound lipidomic shifts that occur in early equine pregnancy, highlighting the critical role of lipid metabolism in supporting embryonic development. These findings provide valuable insights into the metabolic adaptations during these period and potential biomarkers for early pregnancy detection in mares. [ABSTRACT FROM AUTHOR]

A significant fraction of the popular inbred C57Bl/6J mice show structural and biochemical features of the congenital portosystemic shunt (PSS). How this hepatic abnormality affects physiological and behavioural parameters has not been explored in detail. Here, we confirmed the frequent occurrence of the PSS in C57Bl/6J mice by three different methods. We screened a cohort of 119 C57Bl/6J mice for total bile acids (TBA) in plasma, identified 11 animals (9.2%) with high TBA (>11 µm; 171.1 ± 76.8 µm), and confirmed PSS presence in that subset by magnetic resonance angiography and 1H‐magnetic resonance spectroscopy of brain metabolites in the hippocampal area. In addition to the high glutamine and low myo‐inositol levels, we detected lower levels of several neurotransmitters and metabolites in the hippocampus, higher brain weight and volume, as well as enhanced brain glucose utilisation in the PSS mice. We also observed differences in peripheral organ weights, haematological cell counts and clinical chemistry parameters in C57Bl/6J mice with and without PSS. Animals with PSS were slightly hyperlocomotive, had better balance on the rotarod, showed altered gait properties, and displayed attenuated fear memory in the fear conditioning test. Furthermore, we revealed a significant alteration of the pharmacokinetic profile of diazepam in C57Bl/6J mice with PSS. Our data support previous reports of hepatic disturbances and demonstrate an altered neurobiological phenotype in C57Bl/6J mice with PSS. Such congenital differences between inbred C57Bl/6J littermates may significantly distort experimental outcomes of pharmacological, behavioural and genetic studies. Key points: A significant proportion of C57Bl/6J mice, an inbred strain popular in preclinical research, have congenital portosystemic shunts (PSS) that allow venous blood to enter systemic circulation bypassing the liver.In this study, we extended existing knowledge of PSS consequences, particularly with respect to the effects on brain structure and function.We demonstrated that C57Bl/6J mice with PSS differ from their normal counterparts in brain size and contents of several neuroactive substances, as well as in peripheral organ weights, rate of glucose utilisation, blood cell counts and blood clinical chemistry parameters.C57Bl/6J mice with PSS showed altered locomotor behaviour, performed worse in a memory test and had abnormal blood pharmacokinetics of a benzodiazepine drug after a single administration.PSS presence may significantly complicate the interpretation of experiments in C57Bl/6J mice; therefore, we propose that before their use in biomedical studies, these mice should be screened with a simple blood test. [ABSTRACT FROM AUTHOR]

Objective Intrahepatic cholestasis of pregnancy is associated with adverse pregnancy outcomes including intrauterine fetal demise, spontaneous preterm labor, and meconium-stained amniotic fluid. Studies have yet to determine if patients with a history of pregnancy complicated by cholestasis had an association with more severe adverse outcomes in a subsequent pregnancy complicated by cholestasis. Study Design Retrospective cohort study of multiparous, singleton, nonanomalous live gestations complicated by cholestasis at Elmhurst Hospital Center from 2005 to 2019. We compared rates of adverse outcomes in multiparous pregnancies complicated by cholestasis with versus without prior cholestasis. Our primary outcome was rates of spontaneous preterm labor. Our secondary outcomes included rates of iatrogenic preterm birth, meconium-stained amniotic fluid, cesarean delivery for nonreassuring fetal heart tracing. Chi-square and multivariate regression tests were used to determine the strength of association. In all analyses, a p -value less than 0.05 and 95% confidence interval not crossing 1.00 indicated statistical significance. Mount Sinai Icahn School of Medicine Institutional Review Board approval was obtained for this project. Results Of the 795 multiparous pregnancies complicated by cholestasis, 618 (77.7%) had no prior history of cholestasis and 177 (23.3%) had prior history of cholestasis. Multiparous pregnancies with history of cholestasis had higher rates of prior preterm birth, earlier gestational age at diagnosis and delivery, and were more likely to receive ursodeoxycholic acid therapy. Pregnancies with history of cholestasis were not associated with spontaneous preterm labor in subsequent pregnancies with cholestasis, but history of cholestasis was associated with iatrogenic preterm birth and neonatal intensive care unit (NICU) admission. After adjusting for confounders, the association with iatrogenic preterm birth and NICU admission were no longer statistically significant. There was no significant association between history of cholestasis and other adverse obstetric outcomes. Conclusion Findings suggests that history of prior cholestasis is not associated with worsening outcomes in subsequent pregnancies complicated by cholestasis. Key Points Prior cholestasis may not alter risk in subsequent pregnancies. Unclear relationship between cholestasis and hepatobiliary disease. Studies needed to develop cholestasis screening protocol. [ABSTRACT FROM AUTHOR]

Background: Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol‐lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. Methods: A nested case–control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega‐3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. Results: Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50–0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.53–7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. [Correction added on 19 August 2024, after first online publication: In the preceding sentence, the value '3.534' has been changed to '3.54'.]. No associations were observed for the other medications. Conclusions: Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study. This study within the UK Clinical Practice Research Datalink, involving 3719 patients with liver cancer (cases) and 14,876 controls, evaluated the relation between five nonstatin cholesterol‐lowering medications and liver cancer risk. The findings indicate that cholesterol absorption inhibitors are associated with a reduced risk of liver cancer, whereas bile acid sequestrants are associated with an increased risk, and no significant associations were observed for other medications. [ABSTRACT FROM AUTHOR]

Background: The human gut environment undergoes substantial changes as a host ages. This investigation centered on the gut microbiome diversity among patients with severe motor and intellectual disabilities (SMID), examining the association between the gut microbiome composition and physical characteristics with varying levels of diversity. Methods: Fourteen subjects were investigated, with physical and defecation status, blood biochemical test, gut microbiome profiling, and fecal metabolites used to divide the patients into a high-diversity group (HD, eight patients) and a low-diversity group (LD, six patients). Results: Findings indicated that the microbiome of the LD group showed delayed maturation reminiscent of neonates and lactating infants. Analysis of the fecal bile acids (BAs) revealed a markedly diminished proportion of deoxycholic acid in the secondary BAs in the LD group, suggestive of inadequate conversion from primary to secondary BAs. Furthermore, the LD group presented with loose stools. The LD group exhibited a higher degree of physical severity, with all patients bedridden and fed via gastrostomy with only enteral formula received. Conclusions: The composition of the gut microbiome and BAs in the LD group was found to differ from those of healthy individuals and the HD group, indicating a potentially immature gut environment for these individuals. [ABSTRACT FROM AUTHOR]