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Mounting evidence has linked changes in human gut microbiota to proton pump inhibitor (PPI) use. Accordingly, multiple studies have analyzed the gut microbiomes of PPI users, but PPI–microbe interactions are still understudied. Here, we performed a meta-analysis of four studies with available 16S rRNA gene amplicon sequencing data to uncover the potential changes in human gut microbes among PPI users. Despite some differences, we found common features of the PPI-specific microbiota, including a decrease in the Shannon diversity index and the depletion of bacteria from the Ruminococcaceae and Lachnospiraceae families, which are crucial short-chain fatty acid-producers. Through training based on multiple studies, using a random forest classification model, we further verified the representativeness of the six screened gut microbial genera and 20 functional genes as PPI-related biomarkers, with AUC values of 0.748 and 0.879, respectively. Functional analysis of the PPI-associated 16S rRNA microbiome revealed enriched carbohydrate- and energy-associated genes, mostly encoding fructose-1,6-bisphosphatase and pyruvate dehydrogenase, among others. In this study, we have demonstrated alterations in bacterial abundance and functional metabolic potential related to PPI use, as a basis for future studies on PPI-induced adverse effects. [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) has various biological functions and is used extensively as a dietary supplement. Previous studies have shown that the probiotic effects of polysaccharides are closely associated with their molecular properties. The intestinal microbiota has been demonstrated to degrade HA; however, the regulatory effects of different molecular weights (MW) of HA on gut microbiota and metabolites are unknown. In the present study, we performed in vitro fermentation of human-derived feces for three MWs of HA (HA1, 32.3 kDa; HA2, 411 kDa; and HA3, 1510 kDa) to investigate the differences in the fermentation properties of HA with different MWs. We found that gut microbiota can utilize all HAs and, consequently, produce large amounts of short-chain fatty acids (SCFAs). In addition, we showed that all three HA MWs promoted the growth of Bacteroides, Parabacteroides, and Faecalibacterium, with HA1 being more effective at promoting the growth of Bacteroides. HAs have various regulatory effects on the structure and metabolites of the gut microbiota. Spearman's correlation analysis revealed that alterations in gut microbiota and their metabolites were significantly correlated with changes in metabolic markers. For instance, HA1 enriched α-eleostearic acid and DL-3-aminoisobutyric acid by regulating the abundance of Bacteroides, and HA3 enriched Thymidin by regulating Faecalibacterium. Collectively, the fermentation properties of HA vary across MW, and our results provide insights into the potential association between the MW of HA and its fermentation characteristics by the gut microbiota. These findings provide insights into the influence of the gut microbiota and HAs on the health of the host. [ABSTRACT FROM AUTHOR]

As a toxic environmental contaminant, lead (Pb) enters the body via the food chain and leads to a disturbance of the gut microbiota. Lactiplantibacillus plantarum CCFM8661 was found to be favorable in decreasing Pb concentrations in the blood and organs of chronically Pb-ingested mice and in promoting fecal Pb excretion. The alterations of the colonic microbiome as well as the colonic and serum metabolomes of chronically Pb-exposed mice after L. plantarum CCFM8661 intervention were investigated. It was observed that L. plantarum CCFM8661 induced significant changes in α and β diversity, increasing Bacteroides , Bifidobacterium , and Dubosiella , which are regarded as beneficial genera, and decreasing harmful genera such as Bilophila. Untargeted metabolomics identified that L. plantarum CCFM8661 significantly increased serum level of lauric acid as well as colonic levels of taurine and metabolites in the purine metabolism pathway, including xanthine, deoxyinosine, hypoxanthine, guanine, and deoxyguanosine. These metabolites were associated with differential bacteria and contributed to repairing the intestinal barrier and facilitating Pb excretion. It turned out that regulation of gut microbiota and its metabolic activity may be one of the important reasons why L. plantarum CCFM8661 alleviates the symptoms of Pb poisoning. [Display omitted] • L. p lantarum CCFM8661 alleviate Pb toxicity by changing microbiota and metabolites. • Microbial alterations include increase of Bifidobacterium and decrease of Bilophila. • Increased metabolites include taurine and xanthine in colon, lauric acid in serum. • Metabolic pathways include purine metabolism and primary bile acid biosynthesis. [ABSTRACT FROM AUTHOR]

The human gut harbors a dense and highly diverse microbiota of approximately 1,000 bacterial species. The interaction between the host and gut bacteria strongly influences human health. Numerous evidence suggest that intestinal flora imbalance is closely associated with the development and treatment of liver diseases, including acute liver injury and chronic liver diseases (cirrhosis, autoimmune liver disease, and fatty liver). Therefore, regulating the gut microbiota is expected to be a new method for the adjuvant treatment of liver diseases. Fecal microbiota transplantation (FMT) is defined as the transplantation of gut microbiota from healthy donors to sick patients via the upper or lower gastrointestinal route to restore the normal intestinal balance. In this study, we briefly review the current research on the gut microbiota and its link to liver diseases and then summarize the evidence to elucidate the clinical application and development of FMT in liver disease treatment. [ABSTRACT FROM AUTHOR]

The adaptive evolution in indigenous intestinal microbes derived from probiotics is critical to safety and efficacy evaluation of probiotics, yet it is still largely underexplored. Here, through 11 publicly accessible datasets, we demonstrated that probiotic consumption can lead to widespread single-nucleotide variants (SNVs) in the native microbiota. Interestingly, the same probiotic strains introduced far more SNVs in mouse gut than humans. Furthermore, the pattern of probiotics-induced SNVs was highly probiotic-strain specific, and 17 common SNVs in Faecalibacterium prausnitzii genome were identified cross studies, which might lead to changes in bacterial protein structure. Further, nearly 50% of F. prausnitzii SNVs can be inherited for six months in an independent human cohort, whereas the other half only transiently occurred. Collectively, our study substantially extended our understanding of co-evolution of the probiotics and the indigenous gut microbiota, highlighting the importance of assessment of probiotics efficacy and safety in an integrated manner. Chenchen Ma, Chengcheng Zhang, and Denghui Chen et al. examine how probiotic consumption impacts gut microbiota composition in human and mice through a global, cross-cohort metagenomic analysis. Their results suggest that probiotic consumption may result in widespread variation among the native microbiota in both the human and mouse gut. [ABSTRACT FROM AUTHOR]

Lacticaseibacillus rhamnosus is a recognized probiotic that is widely used in scientific research and clinical applications. This study found that the Lacticaseibacillus rhamnosus GG (LGG) strain can reduce the adhesion of Escherichia coli (E. coli) to primary chicken intestinal epithelial cells by 75.7% and inhibit 41.7% of the E. coli that adhere to intestinal epithelial cells. Additionally, LGG showed strong inhibitory ability on the growth of E. coli , Staphylococcus aureus , Salmonella Paratyphi B, and Salmonella Enteritidis in vitro. Furthermore, the influence of LGG on the growth performance, intestinal flora, immunity, and disease resistance of chickens was explored. Chickens fed with LGG exhibited increased average daily weight gain and concentrations of sIgA, IgG, and IgM than did controls. After 21 days of feeding, a diet with LGG increased the diversity of intestinal microbiota and maintained intestinal health. Moreover, LGG promoted immunologic barriers by upregulating cytokines and chemokines via the Toll-like receptor. The major pro-inflammatory factors, including Myd88 , NF- κ B , Il6 , and Il8 , were upregulated compared to controls. After being challenged with E. coli , the survival rate of chickens fed with LGG was significantly higher than those in the control group, and decreased numbers of E. coli were detected in the heart and lungs of the LGG group. In summary, oral administration of LGG to chickens could improve growth performance, maintain intestinal homeostasis, and enhance innate immune response and disease resistance. [ABSTRACT FROM AUTHOR]

Lead (Pb) is a toxic heavy metal, having profound threats to the global population. Multiple organs such as kidney, and liver, as well as nervous, hematologic, and reproductive systems, are commonly considered the targets of Pb toxicity. Increasing researches reported that the effects of Pb on gastrointestinal tracts are equally intensive, especially on intestinal microbiota. This review summarized Pb toxicity on gut physiology and microbiota in different animal models and in humans, of which the alterations may further have effects on other organs in host. To be more specific, Pb can impair gut barrier and increase gut permeability, which make inflammatory cytokines, immunologic factors, as well as microbial metabolites such as bile acids (BA) and short-chain fatty acids (SCFAs) enter the enterohepatic circulation easily, and finally induce multiple systematic lesion. In addition, we emphasized that probiotic treatment may be one of the feasible and effective strategies for preventing Pb toxicity. [ABSTRACT FROM AUTHOR]

Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria , can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum , but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA- dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA -cluster-carrying B. longum , but not an abfA -deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA -cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies. [Display omitted] • abfA cluster-carrying B. longum strains ameliorate functional constipation (FC) • abfA abundance in the fecal microbiomes is predictive of FC in multiple cohorts • Introducing abfA enriches beneficial metabolites of gut residents (e.g., acetate) • abfA cluster is a gut-microbiome therapeutic target for FC in humans Zhang et al. show that B. longum strains possessing the abfA cluster can ameliorate functional constipation (FC) through enhanced arabinan utilization in the gut. Administration of abfA cluster-carrying B. longum -enriched arabinan utilization residents and beneficial metabolites that alleviate FC in both mice and humans suggests therapeutic targets for FC. [ABSTRACT FROM AUTHOR]

[Display omitted] • The relative abundance of Bifidobacterium pseudocatenulatum was significantly higher in vegans than in omnivores. • B. longum , B. adolescentis , and B. pseudocatenulatum differed significantly in carbohydrate metabolism in O, V and VG. • The genes encoding GH29 and GH43_27 of B. longum were significantly enriched in vegans. • B. adolescentis and B. pseudocatenulatum associated with O, had a higher prevalence of the genes encoding GH26 and GH27. Dietary habits contribute to the composition and function of the gut microbiota. Different dietary structures, including vegan, vegetarian, and omnivorous diets, affect intestinal Bifidobacteria; however, the relationship between Bifidobacterial function and host metabolism in subjects with different dietary patterns is unclear. Here, we analyzed five metagenomics studies and six 16S sequencing studies, including 206 vegetarians (VG), 249 omnivores (O), and 270 vegans (V), through an unbiased theme-level meta-analysis framework and discovered that diet significantly affects the composition and functionality of intestinal Bifidobacteria. The relative abundance of Bifidobacterium pseudocatenulatum was significantly higher in V than in O and Bifidobacterium longum , Bifidobacterium adolescentis , and B. pseudocatenulatum differed significantly in carbohydrate transport and metabolism in subjects with different diet types. Diets high in fiber were associated with B. longum with increased capacity for carbohydrate catabolism and genes encoding GH29 and GH43_27 were significantly enriched in V. Bifidobacterium adolescentis and B. pseudocatenulatum , associated with O, had a higher prevalence of the genes related to carbohydrate transport and metabolism, which showed the enrichment of GH26 and GH27 families. The same Bifidobacterium species has different functions in subjects with different diet types, resulting in different physiological significance. The diversification and functionalities of Bifidobacterial species in the gut microbiome can be influenced by the host diet and this aspect should be considered when studying host-microbe associations. [ABSTRACT FROM AUTHOR]

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Hypercholesterolemia is an independent risk factor of cardiovascular disease, which is among the major causes of death worldwide. The aim of this study was to explore whether Bifidobacterium longum strains exerted intra-species differences in cholesterol-lowering effects in hypercholesterolemic rats and to investigate the potential mechanisms. SD rats underwent gavage with each B. longum strain (CCFM 1077, I3, J3 and B3) daily for 28 days. B. longum CCFM 1077 exerted the most potent cholesterol-lowering effect, followed by B. longum I3 and B3, whereas B. longum B3 had no effect in alleviating hypercholesterolemia. Divergent alleviation of different B. longum strains on hypercholesterolemia can be attributed to the differences in bile salt deconjugation ability and cholesterol assimilation ability in vitro. By 16S rRNA metagenomics analysis, the relative abundance of beneficial genus increased in the B. longum CCFM 1077 treatment group. The expression of key genes involved in cholesterol metabolism were also altered after the B. longum CCFM 1077 treatment. In conclusion, B. longum exhibits strain-specific effects in the alleviation of hypercholesterolemia, mainly due to differences in bacterial characteristics, bile salt deconjugation ability, cholesterol assimilation ability, expressions of key genes involved in cholesterol metabolism and alterations of gut microbiota. [ABSTRACT FROM AUTHOR]

Subcritical water can effectively hydrolyze pectin into smaller molecules while still maintaining its functional regions. Pectic heteropolysaccharide can mediate immune regulation; however, the possible effects of subcritical water-hydrolyzed citrus pectin (SCP) on the immune response remain unclear. Therefore, the effects of SCP on immunomodulatory functions and intestinal microbial dysbiosis were investigated using a cyclophosphamide-induced immunosuppressed mouse model. In this research, immunosuppressed ICR mice were administrated with SCP at dosages of 300/600/1200 mg/kg.bw by oral gavage, and body weight, immune organ indexes, cytokines, and gut microbiota were determined. The results showed that subcritical water treatment decreased the molecular mass and increased the content of galacturonic acid in citrus pectin hydrolysates. Meanwhile, the treatment with SCP improved immunoregulatory functional properties and bioactivities over the original citrus pectin. For example, SCP protected immune organs (accelerated recovery of immune organ indexes) and significantly enhanced the expression of immune-related cytokines (IL-2, IL-6, IFN-γ, and TNF-α). The results of the 16S rDNA sequencing analysis on an IlluminaMiSeq platform showed that SCP normalized Cy-induced gut dysbiosis. SCP ameliorated Cy-dependent changes in the relative abundance of several taxa, shifting the balance back to normal status (e.g., SCP increased beneficial Muribaculaceae, Ruminococcaceae, Bacteroidaceae, and Prevotellaceae while decreasing pathogenic Brevundimonas and Streptococcus). The results of this study suggest an innovative application of citrus pectin as an immunomodulator. [ABSTRACT FROM AUTHOR]

While there is strong evidence showing that many food-borne probiotics regulate cholesterol metabolism, few studies have examined how probiotics of human origin affect cholesterol metabolism. Because people living in so-called 'longevity villages' are unlikely to have hypercholesterolemia, we hypothesized that probiotics isolated from the residents would have cholesterol-reducing effects on rats with hypercholesterolemia. We isolated 16 strains of Lactobacillus from four longevity populations in China. The strains were tested in vitro for bile salt hydrolase (BSH) activity and two isolates, Lactobacillus reuteri A9 and Lactobacillus mucosae A13, were screened out. These two strains were then administered daily for 28 d to rats fed a cholesterol-rich diet. The serum total cholesterol levels in the L. reuteri A9 and L. mucosae A13 groups decreased by 24.3% and 21.6%, respectively. The serum low density lipoprotein cholesterol levels decreased by 23.8% and 25.2%, respectively. The L. reuteri A9 and L. mucosae A13 groups also exhibited upregulated hepatic mRNA expression of Sterol regulatory element-binding protein 2 (Srebp2) by 2.71-fold and 2.54-fold, respectively. The mRNA expression levels of hepatic low-density lipoprotein receptor (Ldlr) in the two groups were significantly up-regulated by 1.28-fold and 2.17-fold, respectively. The composition of gut microbiota was recovered by oral gavage in both experimental groups, and the destroyed diversity of gut microbiota was relieved. [ABSTRACT FROM AUTHOR]

[Display omitted] • Degree and efficiency of BG degradation varies with structure. • Bacteroides was promoted by all BGs, but other bacteria varied with the BG structure. • Glycosidic bonding differences in BG lead to changes in gut microbiota and metabolism. • Diversity of bond types induces a wide range of microbiota and metabolic changes. • Potential synergistic degradation BGs may occur among gut bacteria. The gut microbiota is widely acknowledged as a crucial factor in regulating host health. The structure of dietary fibers determines changes in the gut microbiota and metabolic differences resulting from their fermentation, which in turn affect gut microbe-related health effects. β-Glucan (BG) is a widely accessible dietary fiber to humans, and its structural characteristics vary depending on the source. However, the interactions between different structural BGs and gut microbiota remain unclear. This study used an in vitro fermentation model to investigate the effects of BG on gut microbiota, and microbiomics and metabolomics techniques to explore the relationship between the structure of BG, bacterial communities, and metabolic profiles. The four sources of BG (barley, yeast, algae, and microbial fermentation) contained different types and proportions of glycosidic bonds, which differentially altered the bacterial community. The BG from algal sources, which contained only β(1 → 4) glycosidic bonds, was the least metabolized by the gut microbiota and caused limited metabolic changes. The other three BGs contain more diverse glycosidic bonds and can be degraded by bacteria from multiple genera, causing a wider range of metabolic changes. This work also suggested potential synergistic degradation relationships between gut bacteria based on BG. Overall, this study deepens the structural characterization-microbial-functional understanding of BGs and provides theoretical support for the development of gut microbiota-targeted foods. [ABSTRACT FROM AUTHOR]

Aging is a process characterized by a time-dependent decline in the functionality of adult stem cells and is closely associated with age-related diseases. However, understanding how aging promotes disease and its underlying causes is critical for combating aging. The offspring of UAS-Gal4 and CG12744RNAi Drosophila were cultured for 33 days to evaluate the role of CG12744 in the aging intestine. Immunofluorescence was performed to detect specific cell type markers for assessing proliferation and differentiation. qRT–PCR was used to observe the changes in signaling regulating intestinal homeostasis in the aging intestine after CG12744 knockdown. 16S rRNA-seq analysis was also conducted to elucidate the role of gut microbes in CG12744-mediated intestinal dysfunction. The mRNA levels of CG12744 were significantly increased in the aged midguts. Knockdown of CG12744 in progenitor cells further exacerbates the age-related intestinal hyperplasia and dysfunction. In particular, upon depletion of CG12744 in progenitors, enteroblasts (EBs) exhibited an increased propensity to differentiate along the enteroendocrine cell (EE) lineage. In contrast, the overexpression of CG12744 in progenitor cells restrained age-related gut hyperplasia in Drosophila. Moreover, CG12744 prevented age-related intestinal stem cell (ISC) overproliferation and differentiation by modulating the EGFR, JNK, and BMP pathways. In addition, the inhibition of CG12744 resulted in a significant increase in the gut microbial composition in aging flies. This study established a role for the CG12744 in regulating the proliferation and differentiation of adult stem cells, thereby identifying a potential therapeutic target for diseases caused by age-related dysfunction stem cell dysfunction. [ABSTRACT FROM AUTHOR]

[Display omitted] • FOS was slightly better than inulin in modulating the gut microbiota. • H was enriched for butyrate-producing bacteria and butyric acid after FOS intervention. • After inulin intervention, the L was enriched with more glycolytic functions. • H was enriched for amino acids and aminoglycolytic functions after inulin intervention. Prebiotics are known to modulate the gut microbiota, but there is host variability, mainly due to differences in carbohydrate-utilisation by gut microbiota. Bifidobacterium and Bacteroides are powerful carbohydrate-utilising bacteria, and the ratio of both is closely related to the utilisation of prebiotics. However, the differential impact of prebiotics on the composition and function of the gut microbiota and its metabolites in participants with different Bacteroides/Bifidobacterium (Ba/Bi) ratios have not been studied. Here, we conducted a 4-week randomised double-blind, parallel four-arm trial using two prebiotics (oligofructose and inulin) in two populations with high Ba/Bi (H) and low Ba/Bi (L). The response to prebiotics in both populations was influenced by the baseline microbiota background specificity. Notably, at an overall level, FOS was slightly better than inulin in modulating the gut microbiota. Difference in gut microbiota regulation by FOS across microbiota contexts were significant between the two groups. Butyric acid-producing bacteria were significantly more abundant in H and further elevated butyric acid and related metabolite levels, with H more likely to benefit from the FOS intervention. The two groups showed only metabolic differences in their response to inulin, with L showing a significant increase in propionic acid and being enriched in glycolysis functions, whereas H was enriched in amino acids and aminoglycolysis functions. Overall, these results provide a basis for selecting appropriate prebiotics for participants with different gut backgrounds. [ABSTRACT FROM AUTHOR]