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Introduction Gut microbiota has been implicated in the pharmacological activities of many natural products. As an effective hypolipidemic agent, berberine (BBR)’s clinical application is greatly impeded by the obvious inter-individual response variation. To date, little evidence exists on the causality between gut microbes and its therapeutic effects, and the linkage of bacteria alterations to the inter-individual response variation. Objectives This study aims to confirm the causal role of the gut microbiota in BBR’s anti-hyperlipidemic effect and identify key bacteria that can predict its effectiveness. Methods The correlation between gut microbiota and BBR’s inter-individual response variation was studied in hyperlipidemic patients. The causal role of gut microbes in BBR’s anti-hyperlipidemic effects was subsequently assessed by altered administration routes, co-treatment with antibiotics, fecal microbiota transplantation, and metagenomic analysis. Results Three-month clinical study showed that BBR was effectively to decrease serum lipids but displayed an obvious response variation. The cholesterol-lowering but not triglyceride-decreasing effect of BBR was closely related to its modulation on gut microbiota. Interestingly, the baseline levels of Alistipes and Blautia could accurately predict its anti-hypercholesterolemic efficiency in the following treatment. Causality experiments in mice further confirmed that the gut microbiome is both necessary and sufficient to mediate the lipid-lowering effect of BBR. The absence of Blautia substantially abolished BBR's cholesterol-decreasing efficacy. Conclusion The gut microbiota is necessary and sufficient for BBR’s hyperlipidemia-ameliorating effect. The baseline composition of gut microbes can be an effective predictor for its pharmacotherapeutic efficacy, providing a novel way to achieve personalized therapy.

Purpose: To evaluate the safety of the Fecal Microbial Transplant for Sjogren Syndrome (FMT) trial in individuals with immune-mediated dry eye (DE). Design: Open-label, nonrandomized clinical trial. Methods: The study population included 10 individuals with DE symptoms and signs meeting criteria for Sjogren or positive early Sjogren markers. Procedures were 2 FMTs from a single healthy donor delivered via enema, 1 week apart. The primary outcome measure was safety. In addition, gut microbiome profiles, DE metrics, and T-cell profiles in blood were examined at baseline before FMT, and at 1 week, 1 month, and 3 months after FMT. Results: The mean age of the population was 60.4 years; 30% were male; 50% were white; and 50% were Hispanic. At baseline, all subjects had significantly different gut microbiome profiles from the donor, including higher mean diversity indices. Subjects had a decreased abundance of genera Faecalibacterium, Prevotella, and Ruminococcus and an increased abundance of genera Alistipes, Streptococcus, and Blautia compared to the donor. Effector and regulatory T-cell profiles were positively correlated with each other and with DE symptom severity (T helper 1 cells [Th1]; r = .76; P = .01; Th17: r = 0.83; P = .003; CD25: r = 0.66; P = .04; FoxP3: r = 0.68; P = .03). No adverse events were noted with FMT. After FMT, gut microbiome profiles in 8 subjects moved closer to the donor's profile. As a group, gut microbiome profiles at all follow-up time points were more similar to the original recipients’ than the donor's microbiome; however, certain phyla, classes, and genera operational taxonomic unit (OTU) numbers remained closer to the donor vs recipients’ baseline profiles out to 3 months. Five individuals subjectively reported improved dry eye symptoms 3 months after FMT. Conclusions: FMT was safely performed in individuals with immune-mediated DE, with certain bacterial profiles resembling the donor out to 3 months after FMT. One-half the subjects reported improved DE symptoms. The most effective FMT administration method has yet to be determined.

Accumulating evidence has pointed out that the gut-brain axis plays important roles in the etiology of autism spectrum disorder (ASD). Gut dysbiosis was reported in both ASD human patients and animal models. Dip2a was identified as a human ASD candidate gene. Deletion of Dip2a led to dendritic spine dysfunction and autistic-like behaviors in mice. To further investigate if Dip2a deletion leads to gut dysbiosis, we used 16S rDNA sequencing to study the gut microbiota in Dip2a KO mice. In both co-housed and separated breeding conditions, deletion of Dip2a could affect the gut microbiome composition. The probiotic bacteria, Lactobacillus and Bifidobacterium, became less abundant, while some potentially harmful bacteria, Alistipes, Lachnospiraceae_NK4A136_group, Clostridium, Desulfovibrio, and Enterorhabdus, became more abundant. We further found that probiotic treatment could help to reconstitute the gut microbiome composition in Dip2a KO mice. Altogether, these data showed DIP2A is required for the proper composition of gut microbiota, and the probiotics have potential roles in rectifying the gut microbiota in Dip2a KO mice.

We have found that intestinal bacteria and their metabolites, short‐chain fatty acids (SCFAs), promote cancer growth in prostate cancer (PCa) mouse models. To clarify the association between gut microbiota and PCa in humans, we analyzed the gut microbiota profiles of men with suspected PCa. One hundred and fifty‐two Japanese men undergoing prostate biopsies (96 with cancer and 56 without cancer) were included in the study and randomly divided into two cohorts: a discovery cohort (114 samples) and a test cohort (38 samples). The gut microbiota was compared between two groups, a high‐risk group (men with Grade group 2 or higher PCa) and a negative + low‐risk group (men with negative biopsy or Grade group 1 PCa), using 16S rRNA gene sequencing. The relative abundances of Rikenellaceae, Alistipes, and Lachnospira, all SCFA‐producing bacteria, were significantly increased in high‐risk group. In receiver operating characteristic curve analysis, the index calculated from the abundance of 18 bacterial genera which were selected by least absolute shrinkage and selection operator regression detected high‐risk PCa in the discovery cohort with higher accuracy than the prostate specific antigen test (area under the curve [AUC] = 0.85 vs 0.74). Validation of the index in the test cohort showed similar results (AUC = 0.81 vs 0.67). The specific bacterial taxa were associated with high‐risk PCa. The gut microbiota profile could be a novel useful marker for the detection of high‐risk PCa and could contribute to the carcinogenesis of PCa., To clarify the association between the gut microbiota and prostate cancer, we analyzed the gut microbiota profiles of 152 men undergoing prostate biopsy. The abundances of Rikenellaceae, Alistipes, and Lachnospira were significantly increased in men with high‐risk cancer. The index calculated from the abundance of 18 bacterial genera detected high‐risk cancer with higher accuracy than the prostate specific antigen test.

Royal jelly (RJ) and selenium (Se)-rich foods have well-known health benefits which are attributable to a broad range of pharmacologic effects including antioxidant, bacteriostatic, anticancer, and immunoregulatory activities. However, there was no study to combine Se with RJ. Here, Se-rich RJ (SRJ) was produced by feeding sodium selenite to honeybees (Apis mellifera). To further clarify the function of SRJ, mice were then fed RJ or SRJ for 30 days, and their antioxidant capacity and gut microbiota profile were analyzed. The results showed that SRJ treatment could more effectively increase glutathione peroxidase levels in the liver and kidney, as well as total antioxidant activity in the liver and superoxide dismutase level in the kidney. Additionally, the ratio of Firmicutes/Bacteroidetes and relative abundance of the Lachnospiraceae and Prevotellaceae families were increased, whereas the abundance of Helicobacterceae was decreased in mice treated with SRJ. At the genus level, SRJ increased the relative abundance of Lachnospiraceae NK4A136 group, Prevotellaceae UCG 001, Rikenellaceae RC9 gut group, and Oscillibacter and decreased that of Alistipes. And the functional prediction of gut microbiota indicated SRJ treatment could enhance the amino acid metabolism. Correlation analysis indicated that SRJ could optimize the functional network of gut microbiota and the interactions between the gut microbiota and the host. These results suggested the SRJ had potential therapeutic applications in the improvement of overall health or treatment of diseases related to oxidative stress or dysbiosis.

Background Inter-individual variations in gut microbiota composition are observed even among healthy populations. The gut microbiota may exhibit a unique composition depending on the country of origin and race of individuals. To comprehensively understand the link between healthy gut microbiota and host state, it is beneficial to conduct large-scale cohort studies. The aim of the present study was to elucidate the integrated and non-redundant factors associated with gut microbiota composition within the Japanese population by 16S rRNA sequencing of fecal samples and questionnaire-based covariate analysis. Results A total of 1596 healthy Japanese individuals participated in this study via two independent cohorts, NIBIOHN cohort (n = 954) and MORINAGA cohort (n = 642). Gut microbiota composition was described and the interaction of these microorganisms with metadata parameters such as anthropometric measurements, bowel habits, medical history, and lifestyle were obtained. Thirteen genera, including Alistipes, Anaerostipes, Bacteroides, Bifidobacterium, Blautia, Eubacterium halli group, Faecalibacterium, Fusicatenibacter, Lachnoclostridium, Parabacteroides, Prevotella_9, Roseburia, and Subdoligranulum were predominant among the two cohorts. On the basis of univariate analysis for overall microbiome variation, 18 matching variables exhibited significant association in both cohorts. A stepwise redundancy analysis revealed that there were four common covariates, Bristol Stool Scale (BSS) scores, gender, age, and defecation frequency, displaying non-redundant association with gut microbial variance. Conclusions We conducted a comprehensive analysis of gut microbiota in healthy Japanese individuals, based on two independent cohorts, and obtained reliable evidence that questionnaire-based covariates such as frequency of bowel movement and specific dietary habit affects the microbial composition of the gut. To our knowledge, this was the first study to investigate integrated and non-redundant factors associated with gut microbiota among Japanese populations.

Background Lactulose was one of the earliest prebiotics to be identified. To assess the potential risk of large intakes of lactulose to the intestinal microbiota, mice were fed a diet containing lactulose (0%, 5% and 15%, w/w) for 2 weeks and the changes in the fecal microbiota were evaluated by 16S rRNA high-throughput sequencing. Results Lactulose intervention decreased the α-diversity of the fecal microbiota in both low-dose and high-dose groups. The relative abundance of Actinobacteria was significantly increased, while that of Bacteroidetes was significantly decreased after lactulose intervention. At the genus level, the relative abundance of Bifidobacterium belonging to Actinobacteria was significantly increased, and that of Alistipes belonging to Bacteroidetes was decreased in both low-dose and high-dose groups. The relative abundance of Blautia was significantly increased from 0.2% to 7.9% in the high-dose group and one strain of Blautia producta was isolated from the mice feces. However, the strain could not utilize lactulose. Conclusion Overall, the microbial diversity was decreased after lactulose treatment, with significant increases in the relative abundance of Bifidobacterium. We also provide a strategy to increase the relative abundance of Blautia in the intestine by lactulose feeding at high doses, although the mechanism is not revealed. This will help us understand the prebiotic effect of lactulose on the host health. © 2021 Society of Chemical Industry.

Short-term or acute temperature stress affect the immune responses and alters the gut microbiota of broilers, but the influences of long-term temperature stress on stress biomarkers and the intestinal microbiota remains largely unknown. Therefore, we examined the effect of three long-term ambient temperatures (high (HC), medium (MC), and low (LC) temperature groups) on the gene expression of broilers’ heat shock proteins (Hsps) and inflammation – related genes, as well as the caecal microbial composition. The results revealed that Hsp70 and Hsp90 levels in HC group significantly increased, and levels of Hsp70, Hsp90, IL-6, TNF-α, and NFKB1 in LC group were significantly higher than in MC group (p < 0.05). In comparison with the MC group, the proportion of Firmicutes increased in HC and LC groups, while that of Bacteroidetes decreased in LC group at phylum level (p < 0.05). At genus level, the proportion of Escherichia/Shigella, Phascolarctobacterium, Parabacteroides,and Enterococcus increased in HC group; the fraction of Faecalibacterium was higher in LC group; and the percentage of Barnesiella and Alistipes decreased in both HC and LC groups (p < 0.05). Functional analysis based on communities’ phylogenetic investigation revealed that the pathways involved in environmental information processing and metabolism were enriched in the HC group. Those involved in cellular processes and signaling, metabolism, and gene regulation were enriched in LC group. Hence, we conclude that the long-term temperature stress can greatly alter the intestinal microbial communities in broilers and may further affect the host’s immunity and health.

Background Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T cells in the blood as well as inflammation and fibrosis in various organs, but they have no established etiologies. Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors. Methods The gut microbiomes from IgG4-RD and SSc patients as well as healthy individuals with no recent antibiotic treatment were studied by metagenomic sequencing of stool DNA. De novo assembly-based taxonomic and functional characterization, followed by association and accessory gene set enrichment analysis, were applied to describe microbiome changes associated with both diseases. Results Microbiomes of IgG4-RD and SSc patients distinctly separated from those of healthy controls: numerous opportunistic pathogenic Clostridium and typically oral Streptococcus species were significantly overabundant, while Alistipes, Bacteroides, and butyrate-producing species were depleted in the two diseases compared to healthy controls. Accessory gene content analysis in these species revealed an enrichment of Th17-activating Eggerthella lenta strains in IgG4-RD and SSc and a preferential colonization of a homocysteine-producing strain of Clostridium bolteae in SSc. Overabundance of the classical mevalonate pathway, hydroxyproline dehydratase, and fibronectin-binding protein in disease microbiomes reflects potential functional differences in host immune recognition and extracellular matrix utilization associated with fibrosis. Strikingly, the majority of species that were differentially abundant in IgG4-RD and SSc compared to controls showed the same directionality in both diseases. Compared with multiple sclerosis and rheumatoid arthritis, the gut microbiomes of IgG4-RD and SSc showed similar signatures; in contrast, the most differentially abundant taxa were not the facultative anaerobes consistently identified in inflammatory bowel diseases, suggesting the microbial signatures of IgG4-RD and SSc do not result from mucosal inflammation and decreased anaerobism. Conclusions These results provide an initial characterization of gut microbiome ecology in fibrosis-prone IgG4-RD and SSc and reveal microbial functions that offer insights into the pathophysiology of these rare diseases.

Background: The microbiota plays an important role in host health. Although rubidium (Rb) has been used to study for depression and cancers, the interaction between microbial commensals and Rb is still unexplored. To gain the knowledge of the relationship between Rb and microbes, 51 mice receiving RbCl-based treatment and 13 untreated mice were evaluated of their characteristics and bacterial microbiome changes.Results: The 16S ribosomal RNA gene sequencing of feces showed RbCl generally maintained fecal microbial community diversity, while the shifts in fecal microbial composition were apparent after RbCl exposure for the first time. RbCl significantly enhanced the abundances of Rikenellaceae, Alistipes, Clostridium XlVa and sulfate-reducing bacteria including Deltaproteobacteria, Desulfovibrionales, Desulfovibrionaceae and Desulfovibrio. While, RbCl significantly inhibited the abundances of Tenericutes, Mollicutes, Anaeroplasmatales, Anaeroplasmataceae and Anaeroplasma lineages. Besides, with regarding to the composition of archaea, RbCl significantly enhanced the abundances of Crenarchaeota, Thermoprotei, Sulfolobales, Sulfolobaceae and Sulfolobus lineages. Conclusions: These results revealed that enrichments of Clostridium XlVa and Alistipes could affect the levels of serotonin, a critical signaling molecule of brain-gut-microbiota axis. Therefore, anticancer and anti-depressant effects of RbCl might be partly mediated by modifying brain-gut-microbiota axis.

We previously showed that Lactobacillus brevis-derived polyphosphate (poly P) exerts a curative effect on intestinal inflammation. However, whether or not poly P improves the inflammation and injury of distant organs remains unclear. We aimed to investigate the change in the intestinal microbiome and to evaluate the protective effect of poly P on injuries in a cerulein-induced acute pancreatitis (AP) mouse. Poly P was orally administered to BALB/C mice every day for 24 days, and then mice were intraperitoneally injected with cerulein. Before cerulein injection, stool samples were collected and analyzed by 16S rRNA gene sequencing. Mice were sacrificed at 24 h after the last cerulein injection; subsequently, the serum, pancreas, and colon were collected. The microbial profile differed markedly between poly P and control group. Notably, the levels of beneficial bacteria, including Alistipes and Candidatus_Saccharimonas, were significantly increased, while those of the virulent bacteria Desulfovibrio were decreased in the poly P group. The elevations of the serum amylase and lipase levels by cerulein treatment were suppressed by the pre-administration of poly P for 24 days, but not for 7 days. The numbers of cells MPO-positive by immunohistology were decreased and the levels of MCP-1 significantly reduced in the AP + Poly P group. An immunofluorescence analysis showed that the ZO-1 and occludin in the colon was strongly augmented in the epithelial cell membrane layer in the AP + Poly P group. Poly P attenuates AP through both modification of the intestinal microbiome and enhancement of the intestinal barrier integrity.

The cecal microbiota plays a critical role in energy harvest and nutrient digestion, influencing intestinal health and the performance of chickens. Feed efficiency (FE) is essential for improving economic efficiency and saving social resources in chicken production and may be affected by the cecal microbiota. Therefore, to investigate the composition and functional capacity of cecum microbes related to FE in Xiayan chicken, an indigenous breed in Guangxi province, metagenome sequencing was performed on chicken cecal contents. 173 male and 167 female chickens were divided into high and low FE groups according to the residual feed intake. The cecal microbial genome was extracted and sequenced. The results showed that the genera Bacteroides, Prevotella, and Alistipes were the 3 most abundant in each cecal microbiome. The linear discriminant analysis effect size revealed 6 potential biomarkers in male and 14 in female chickens. Notably, the relative abundance of Lactobacillus in the high FE group was higher than that of the low FE group both in the male and female chickens, and the species Limosilactobacillus oris has a higher score in the high FE group of male chickens. In contrast, some potentially pathogenic microorganisms such as Campylobacter avium in females and Helicobacter pullorum in males were enriched in the low FE group. Predictive functional analysis showed that the high FE group in male chickens had a greater ability of xenobiotics biodegradation and metabolism and signaling molecules and interaction. In addition, the host sex was found to exert effects on the cecal microbial composition and function associated with FE. These results increased our understanding of the cecal microbial composition and identified many potential biomarkers related to FE, which may be used to improve the FE of the chickens.

Background Although recent studies have indicated that intestinal microbiota dweller are involved in the pathogenesis of allergy rhinitis (AR), the influence of gut microbiota on AR adult has not been fully elucidated yet. Hence, we carried out this study to uncover the distinctive bacterial taxa that differentiate allergy rhinitis patients from healthy individuals. Feces samples from thirty three AR patients and thirty one healthy individuals were analyzed by 16S rRNA gene sequencing. Results Results showed that the bacterial diversity in AR group was significantly higher than that of the non-AR group. Bacterial communities between AR and non-AR group were significantly differentiated as revealed by Principal coordinates analysis (PCoA) and the variation within non-AR were higher than that of the counterpart. Firmicutes, Fusobacteria, Actinobacteria, Cyanobacteria and Chloroflexi were the significantly differed phyla taxa and the top significantly distinguished bacterial genus included Prevotella_9, Phascolarctobacterium, Roseburia, Megamonas, Alistipes, Lachnoclostridium and Fusobacterium. The higher network complexity in AR group were dominated by taxa belonging to Firmicutes. The predicted function, alpha linolenic acid metabolism and bacterial invasion of epithelial cells pathway were higher in non-AR group while gonadotropin-releasing hormone (GnRH) signaling pathway, Fc γ-R mediated phagocytosis and endocytosis were higher in AR patients. Although the bacterial diversity between moderate and severe AR patients showed no significant difference, the significant correlation between featured genus and total nasal symptom score or rhinoconjunctivitis quality of life questionnaire, such as Butyricicoccus and Eisenbergiella, revealed the potential to intervene the AR status by means of gut microbiota. Conclusions In conclusion, patients with allergy rhinitis had distinguished gut microbiota characteritics in comparison with healthy controls. The results suggest that gut microbiota might play crucial roles in influencing the course and different symptoms of AR. Trial registration ChiCTR, ChiCTR1900028613. Registered 29 December 2019, https://www.chictr.org.cn/showproj.aspx?proj=47650.

Background Accumulating evidence infer that gut microbiome-host relations are key mediators or modulators driving the observed sexual dimorphism in some disease onset and progression. To date, the sex-differences of gut microbiota at different pubertal status have not been reported. Objective To determine the characteristics of gut microbiota of both genders at different pubertal status. Methods Gut microbiota was analyzed in 89 Chinese participants aged 5–15 years. Participants were divided into pre-puberty and puberty groups for both male and female. The composition of gut microbiota was investigated by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed. The prediction of metagenomic functional content from 16S rRNA gene surveys was conducted. Results There were 49 males (9.76 ± 2.15 years) and 40 females (9.74 ± 1.63 years); 21 males and 26 females were at puberty. At genus level, Alistipes, Megamonas, Oscillospira and Parabacteroides were more prevalent in girls than in boys (p Dorea, Megamonas, Bilophila, Parabacteroides and Phascolarctobacterium as microbial markers for pubertal subjects. The predicted metabolic profiles differ in both pubertal and pre-pubertal groups between genders. Conclusion This cross-sectional study revealed that sex differences in the gut microbiota composition and predicted metabolic profiles exist before puberty, which become more significant at puberty. The identification of novel puberty bacterial markers may disclose a potential effects of gender-related microbiota profiles on puberty onset.

Atrial fibrillation (AF) reduces the quality of life by triggering stroke and heart failure. The association between AF onset and gut metabolites suggests a causal relationship between AF and gut microbiota dysbiosis; however, the relationship remains poorly understood. We prospectively enrolled 34 hospitalized patients with AF and 66 age-, sex-, and comorbidity-matched control subjects without a history of AF. Gut microbial compositions were evaluated by amplicon sequencing targeting the 16S ribosomal RNA gene. We assessed differences in dietary habits by using a brief-type self-administered diet history questionnaire (BDHQ). Gut microbial richness was lower in AF patients, although the diversity of gut microbiota did not differ between the two groups. At the genus level,Enterobacterwas depleted, whileParabacteroides,Lachnoclostridium,Streptococcus,andAlistipeswere enriched in AF patients compared to control subjects. The BDHQ revealed that the intake of n-3 polyunsaturated fatty acids and eicosadienoic acid was higher in AF patients. Our results suggested that AF patients had altered gut microbial composition in connection with dietary habits.

In this study, an alkali-soluble polysaccharide (ASALP) from Arctium lappa L. were extracted and purified. Our results indicated that ASALP was a homogeneous polysaccharide with a molecular weight of 1.2 × 105 Da composed of rhamnose, arabinose, xylose, glucose and galactose in a molar ratio of 1.2: 4.4: 0.9: 0.9: 2.6. The structure characterization indicated that ASALP was mainly consisted of →5-α-L-Araf-(1 → backbone and α-Araf-(1→,→2)-α-Rhap-(1 → T-Glcp-(1→, →3)-β-D-Xylp-(1 → 4)-α-GalpA-(1 → branches. In vitro and in vivo assay showed that ASALP could effectively alleviate inflammation by improving the dysregulation of pro-inflammatory and anti-inflammatory cytokines. Specifically, ASALP significantly inhibited the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) in lipopolysaccharide (LPS)-treated macrophages and in the serum of inflammatory mice, but increased the production of the anti-inflammatory cytokines IL-10. The results from 16S rRNA (V3-V4) amplicon sequencing showed that the relative abundance of Firmicutes, Alistipes, Odoribacter and Lactobacillus in mice was significantly increased after ASALP treatment. Lower levels of Proteobacteria, Staphylococcus and Bacteroidetes were detected in LPS + ASALP treatment group. ASALP alleviated inflammation by improving the reduction of microbial diversity and affecting the composition of the gut microbiota. Our study could provide the basis for the subsequent research and application of ASALP.

Dendrobium officinale Kimura et Migo (D. officinale) is a famous traditional Chinese medicine (TCM). A mixture of D. officinale and American ginseng has been shown to enhance cell-mediated immunity, humoral immunity, and monocyte/macrophage functions in mice. Here, the effects of a D. officinale and American ginseng mixture on the structure of gut microbial community in dogs were examined using high-throughput 16S rRNA gene amplicon sequencing. The data revealed that while the mixture did not change the diversity of gut microbial community significantly, differences among individuals were significantly reduced. Furthermore, the mixture-responsive operational taxonomic units (OTUs) exhibited a phase-dependent expression pattern. Fifty-five OTUs were found to exhibit a mixture-induced expression pattern, among which one third were short-chain fatty acid (SCFA)-producing genera and the others were probiotic genera included Lactobacillus spp., Sutterella, Alistipes, Anaerovorax, Bilophila, Coprococcus, Gordonibacter, Oscillibacter, among others. By contrast, 36% of the OTUs exhibiting a mixture-repressed expression pattern were disease-associated microorganisms, and six genera, namely Actinomyces, Escherichia/Shigella, Fusobacterium, Slackia, Streptococcus and Solobacterium, were associated with cancer. In addition, five genera were closely associated with diabetes, namely Collinsella, Rothia, Howardella, Slackia and Intestinibacter. Our results indicate that this D. officinale and American ginseng mixture may be used as a prebiotic agent to enhance SCFA-producing genera and prevent gut dysbiosis.

High-fat diet (HFD)-induced obesity has been associated with alteration of gut microbiota alongside body weight gain. In this study, the synbiotic effect of Lactobacillus gasseri 505 (LG) and Cudrania tricuspidata (CT) in HFD-induced mice was revealed. After feeding mice with high-fat diet for 10 weeks, combination of LG and CT (LG_CT) exhibited the greatest reduction in the final body weight (11.9%). Moreover, microbial diversity significantly increased, and Principal Coordinate Analysis (PCoA) revealed that the LG_CT group showed closer cluster to NORM. At phylum level, the Firmicutes/Bacteroidetes (F/B) ratio increased in HFD, and the abundance of Bacteroidetes was restored by LG and CT. At genus level, notable changes in Alistipes, Desulfovibrio, Bilophila, and Acetatifactor were observed. Helicobacter elevated to 16.2% in HFD and diminished dramatically to less than 0.01% in LG and/or CT. At species level, L. gasseri increased after the administration of LG (0.54%) and LG_CT (1.14%), suggesting that LG may grow and colonize in the gut and CT can function as a prebiotic. Finally, functional analysis revealed certain metabolic factors correlated with body weight and gut microbiota. This study serves as a potential basis for the application of L. gasseri 505 and C. tricuspidata in the prevention and treatment of diet-induced obesity. Key Points • Combination of L. gasseri (LG) and C. tricuspidata (CT) reduced body weight gain. • Microbial diversity significantly increased in LG_CT treatment. • Abundance of microorganisms involved with leanness increased in LG, CT, and LG_CT. • Body weight is associated with some metabolic functions of gut microbiota.

The protection of Lactobacillus plantarum JM113 against deoxynivalenol (DON)-induced apoptosis and intestinal inflammation on the jejunum of broiler chickens and the potential roles of gut microbiota were determined. A total of 144 one-day-old male broilers (Arbor Acres) were randomly divided into 3 treatment groups consisting of 6 replicates with 8 birds per replicate, including the CON (basal diet), the DON (basal diet + 10 mg/kg DON), and the DL (basal diet + 10 mg/kg DON + 1 × 109 CFU/kg L. plantarum JM113). The DON-diet decreased (P < 0.05) the mRNA expression of mucosal defense proteins and mechanistic target of rapamycin pathway genes. Meanwhile, DON challenge significantly increased Bcl-2-associated X gene/B-cell lymphoma 2 gene (Bcl-2) in the jejunum (P < 0.05) and demonstrated proapoptosis status. In contrast, the DL group showed normal immunity-related gene expression of jejunal mucosa and manifested a superior antiapoptosis status. Adding L. plantarum JM113 significantly raised (P < 0.05) propionic acid, n-butyric acid, and total short-chain fatty acids concentrations in cecal contents of birds fed with DON diet. In addition, DON exposure altered bacterial community structure and disturbed the abundance of several bacterial phyla, families, and genera, leading to dysbiosis. Supplementation with JM113 shifted the gut microbiota composition to that of the CON group. Finally, Spearman correlation analysis suggested that most positive correlations with the mRNA expression of immunity-related and apoptosis-regulatory gene were observed within the phylum Bacteroidetes, and most negative correlations with the indicators were observed within the phylum Firmicutes. The mRNA expression of Bcl-2, TLR2, mTOR, Raptor, and RPS6KB1 (P < 0.05), which are regarded as important cell proliferation and antiapoptosis parameters, were significantly negatively associated with the relative abundances of norank_f__Erysipelotrichaceae, Subdoligranulum, and Anaeroplasma, whereas they had a strong positive correlation with Ruminococcaceae_UCG-004, Alistipes, and Ruminococcaceae_NK4A214_group. These results implied that L. plantarum JM113 supplementation could ameliorate DON-induced apoptosis and intestinal inflammation via manipulating the bacterial community composition and could be used as a potential candidate to attenuate intestinal impairments.

Type 2 resistant starch (RS2) is a fermentable dietary fiber conferring health benefits. We investigated the effects of RS2 on host, gut microbiota, and metabolites in aged mice on high-fat diet. In eighteen-month old mice randomly assigned to control, high-fat (HF), or high-fat+20% RS2 (HFRS) diet for 16 weeks, RS2 reversed the weight gain and hepatic steatosis induced by high-fat diet. Serum and fecal LPS, colonic IL-2 and hepatic IL-4 mRNA expressions decreased while colonic mucin 2 mRNA and protein expressions increased in the HFRS compared to the HF and the control group. 16s rRNA sequencing of fecal microbial DNA demonstrated that RS2 decreased the abundance of pathogen taxa associated with obesity, inflammation, and aging including Desulfovibrio (Proteobacteria phylum), Ruminiclostridium 9, Lachnoclostridium, Helicobacteria, Oscillibacter, Alistipes, Peptococcus, and Rikenella. Additionally, RS2 increased the colonic butyric acid by 2.6-fold while decreasing the isobutyric and isovaleric acid levels by half compared to the HF group. Functional analyses based on Clusters of Orthologous Groups showed that RS2 increased carbohydrate while decreasing amino acid metabolism. These findings demonstrate that RS2 can reverse weight gain, hepatic steatosis, inflammation, and increased intestinal permeability in aged mice on high-fat diet mediated by changes in gut microbiome and metabolites.

This systematic review investigated the effects of ultra-processed very low-energy diets on gut microbiota and metabolic outcomes in individuals with obesity. MEDLINE complete, EMBASE, Scopus, Cochrane and CINAHL were searched between date of inception and October 2019. Seven trials were reviewed (a total of 130 participants, with 10 to 44 participants in each trial). Of these, five were single-arm interventions and included very low-energy diets adjunctive to comprehensive lifestyle interventions such as nutritional counselling, behavioural therapy and exercise programmes. Changes to taxa within the Firmicutes phylum were found, including reduced abundance of potentially beneficial butyrogenic microbes (Roseburia, Faecalbacterium prausnitzii, Lactobacillus, Bifidobacterium and Lachnospiraeceae). Conversely, increased abundance of potentially pathogenic or opportunistic microbes from the Bacteroidetes phylum was reported, including increases in Alistipes and Bacteroides taxa. However, outcomes were inconsistent, with some trials also showing decreases in Bacteroides taxa and increases in commensal microbiota, such as Lachnospiraceae and Bifidobacteriaceae. The changes in metabolic parameters observed from baseline to after the ultra-processed very low-energy diets were mostly beneficial or were not significantly altered. Although the selected articles were deemed to have satisfactory methodological quality, to understand the possible direct effects of these regimens on gut microbiota, further rigorously designed trials, with more standardised microbiological sequencing techniques and detailed reporting, are required. Study registration: Prospero ID: CRD42019124436.

We investigated the gut microbiome in subjects with erectile dysfunction (ED) in a community-based population. This cross-sectional study surveyed comprehensive health status in 408 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. The gut microbiome was assessed by tag sequencing of the 16S rRNA gene, which we extracted from fecal samples. Erectile function was evaluated with the five-item International Index of Erectile Function (IIEF-5), and the men were divided into two groups: low-IIEF-5 (≤ 16) and high-IIEF-5 (> 16). Of those, we selected age-adjusted 192 men (96 each) for analysis. We investigated the association of gut microbiome with IIEF-5 between the two groups. Median age was 50 years. No significant difference was seen in the history of hypertension, DM, CKD, and CVD between the low-IIEF-5 and high-IIEF-5 groups. However, the relative abundance of Alistipes (related with anti-inflammation) and Clostoridium XVIII (related with bowel movement) was significantly different between the two groups. Multivariate logistic analysis demonstrated that the relative abundance of Clostridium XVIII (OR, 2.06; 95% CI, 1.20–3.55, P = 0.009) and Alistipes (OR, 0.81; 95% CI, 0.66–0.99, P = 0.040) and, with an IPSS ≥ 8, were independent factors for low IIEF-5. We observed significant association between the low-IIEF-5 and high-IIEF-5 groups in Alistipes and Clostoridium XVIII. Further study is necessary to access the causal relationship between the gut microbiome and ED.

Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.

Prednisone (PRED) is a synthetic glucocorticoid (GC) widely used in immune-mediated diseases for its immunosuppressive and anti-inflammatory properties. The effects of GC are achieved by genomic and nongenomic mechanisms. However, the nongenomic effects are largely unknown. Thus, we aimed to investigate how long-term prednisone therapy changes the composition of the gut microbiota and fecal metabolites in rats. Male Sprague-Dawley rats were randomly assigned to a control (CON) group and a PRED group, which received prednisone treatment daily for 6 weeks by gavage. The V3 to V4 regions of bacterial 16S rRNA genes were amplified and sequenced after the total bacterial DNA was extracted from fecal samples. The alpha and beta diversities were calculated. The compositional alteration of the gut microbiota at different taxonomic levels was analyzed using the Metastats method. Meanwhile, the fecal metabolites were quantitated in an ultra-performance liquid chromatography system. Similar microbial richness and diversity between the CON and PRED groups were indicated by the alpha diversity results. The gut microbial communities differed significantly between two groups. The relative abundances of the genera Eisenbergiella, Alistipes, and Clostridium XIVb decreased, whereas that of Anaerobacterium increased significantly in rats after the 6-week prednisone treatment. In total, 11 downregulated and 10 upregulated fecal metabolites were identified. Differential fecal metabolites were enriched in the pathways, including phenylalanine metabolism, butanoate metabolism, and propanoate metabolism. The lowered production of short-chain fatty acids was associated with the decreased relative abundance of the genera Alistipes and Clostridium XIVb and increased abundance of the genus Anaerobacterium. The composition of the gut microbiota and fecal metabolites was changed after long-term prednisone treatment. This may help us to understand the pharmacology of prednisone. IMPORTANCE Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver. Prolonged GC therapy causes anti-inflammatory effects; it also results in a variety of adverse events, including obesity, hypertension, psychiatric symptoms, and dyslipidemia. The therapeutic effects and adverse events of GCs may be associated with changes in the gut microbiota, as the host might be affected by the metabolites generated by the altered gut microbes. Thus, we investigated how long-term prednisone therapy changed the composition of the gut microbiota and fecal metabolites in rats. This study may shed new light on the pharmacology of prednisone.

Impaired exercise tolerance and lung function is a marker for increased mortality in lung cancer patients undergoing lung resection surgery. Recent data suggest that the gut-lung axis regulates systemic metabolic and immune functions, and microbiota might alter exercise tolerance. Here, we aimed to evaluate the associations between gut microbiota and outcomes in lung cancer patients who underwent lung resection surgery. We analysed stool samples, from 15 early-stage lung cancer patients, collected before and after surgical resection using shotgun metagenomic and Internal Transcribed Spacer (ITS) sequencing. We analysed microbiome and mycobiome associations with post-surgery lung function and cardiopulmonary exercise testing (CPET) to assess the maximum level of work achieved. There was a significant difference, between pre- and post-surgical resection samples, in microbial community functional profiles and several species from Alistipes and Bacteroides genus, associated with the production of SCFAs, increased significantly in abundance. Interestingly, an increase in VO2 coincides with an increase in certain species and the "GABA shunt" pathway, suggesting that treatment outcome might improve by enriching butyrate-producing species. Here, we revealed associations between specific gut bacteria, fungi, and their metabolic pathways with the recovery of lung function and exercise capacity.

PurposeSleeve gastrectomy (SG) is a surgical intervention for polycystic ovary syndrome (PCOS), especially for patients with obesity. Here, we explored the effects of SG on the gut microbiota of rats with PCOS and investigated the association between the intestinal flora and efficacy of SG in PCOS.MethodsDehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat diet to induce PCOS in rats. SG was performed in rats with PCOS, and the effects of SG on the fecal and gut microbiota and the short-chain fatty acid (SCFA) content were observed. Furthermore, the association among gut microbiota, SCFA content and hyperandrogenism or other hallmarks of PCOS was evaluated.ResultsThe abundance of Firmicutes reduced and that of Bacteroidetes increased in response to SG in the DHEA-induced PCOS rat model. At the genus level, the abundances of Bacteroides and Blautia increased and those of Ruminococcus, Clostridium, and Alistipes reduced distinctly in the PCOS-SG groups. Moreover, the levels of fecal SCFAs, especially butyric acid, reduced after SG. SG significantly ameliorated PCOS-related symptoms such as hyperandrogenism, disrupted ovary function, and impaired glucose tolerance. Bacteroides and Blautia exhibited a negative correlation and Ruminococcus, Clostridium, and Alistipes exhibited a positive correlation with the levels of fecal SCFAs, luteinizing hormone, testosterone, and inflammatory factors.ConclusionsThe amelioration of PCOS-related reproductive and metabolic disorders following SG was associated with the regulation of microbial taxa and SCFA content. Our findings provide a novel perspective on the microbial mechanisms in PCOS after SG.

Patterns of diurnal activity differ substantially between individuals, with early risers and late sleepers being examples of extreme chronotypes. Growing evidence suggests that the late chronotype significantly impacts the risk of developing mood disorders, obesity, diabetes, and other chronic diseases. Despite the vast potential of utilizing chronotype information for precision medicine, the factors that shape chronotypes remain poorly understood. Here, we assessed whether chronotypes are associated with different gut microbiome composition. Using metagenomic sequencing, we established a distinct signature associated with chronotype that involves two bacterial genera Alistipes (elevated in “larks”) and Lachnospira (elevated in “owls”). We have identified four metabolic pathways (e.g. gluconegonesis) that were associated with early chronotype. Significance Statement Studies in recent years uncover a significant relationship between the circadian system and the composition of the gut microbiota. However, the extent to which microbiome variability is associated with individual diurnal timing in humans (chronotype) is unknown. In this study we employed metagenomic sequencing and identified for the first time, a distinct microbiome signature that differs between early and late chronotypes. Given that the microbiome has been shown to be directly linked with food consumption and diet, this study may pave the way for diet-driven interventions aimed to ameliorate health problems associated with extreme chronotypes.

The gut microbiome has been speculated to modulate feeding behavior through multiple factors, including short-chain fatty acids (SCFA). Evidence on this relationship in humans is however lacking. We aimed to explore if specific bacterial genera relate to eating behavior, diet, and SCFA in adults. Moreover, we tested whether eating-related microbiota relate to treatment success in patients after Roux-en-Y gastric bypass (RYGB). Anthropometrics, dietary fiber intake, eating behavior, 16S-rRNA-derived microbiota, and fecal and serum SCFA were correlated in young overweight adults (n = 27 (9 F), 21–36 years, BMI 25–31 kg/m2). Correlated genera were compared in RYGB (n = 23 (16 F), 41–70 years, BMI 25–62 kg/m2) and control patients (n = 17 (11 F), 26–69 years, BMI 25–48 kg/m2). In young adults, 7 bacteria genera, i.e., Alistipes, Blautia, Clostridiales cluster XVIII, Gemmiger, Roseburia, Ruminococcus, and Streptococcus, correlated with healthier eating behavior, while 5 genera, i.e., Clostridiales cluster IV and XIVb, Collinsella, Fusicatenibacter, and Parabacteroides, correlated with unhealthier eating (all | r | > 0.4, FDR-corrected p

Gut microbiota disorder will lead to intestinal damage. This study evaluated the influence of total diterpenoids extracted from Euphorbia pekinensis (TDEP) on gut microbiota and intestinal mucosal barrier after long‐term administration, and the correlations between gut microbiota and intestinal mucosal barrier were analysed by Spearman correlation analysis. Mice were randomly divided to control group, TDEP groups (4, 8, 16 mg/kg), TDEP (16 mg/kg) + antibiotic group. Two weeks after intragastric administration, inflammatory factors (TNF‐α, IL‐6, IL‐1β) and LPS in serum, short chain fatty acids (SCFAs) in feces were tested by Enzyme‐linked immunosorbent assay (ELISA) and high‐performance liquid chromatography (HPLC), respectively. The expression of tight junction (TJ) protein in colon was measured by western blotting. Furthermore, the effects of TDEP on gut microbiota community in mice have been investigated by 16SrDNA high‐throughput sequencing. The results showed TDEP significantly increased the levels of inflammatory factors in dose‐dependent manners, and decreased the expression of TJ protein and SCFAs, and the composition of gut microbiota of mice in TDEP group was significantly different from that of control group. When antibiotics were added, the diversity of gut microbiota was significantly reduced, and the colon injury was more serious. Finally, through correlation analysis, we have found nine key bacteria (Barnesiella, Muribaculaceae_unclassified, Alloprevotella, Candidatus_Arthromitus, Enterorhabdus, Alistipes, Bilophila, Mucispirillum, Ruminiclostridium) that may be related to colon injury caused by TDEP. Taken together, the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors., The total diterpenoids were extracted and isolated from the radix of Euphorbia pekinensis (TDEP), and it’s influence on gut microbiota and intestinal mucosal barrier were evaluated. Correlation analysis was conducted to find out key microbiota. In conclusion, we found the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors.

Atopic dermatitis (AD) is a common inflammatory skin disease. This study aims to investigate the effect of azithromycin (AZI) pretreatment, a common macrolide-type antibiotic, on the trimellitic anhydride (TMA) induced AD-like symptoms in mice. AZI (25 mg/kg, once daily, 5 days) was administered intragastrically before the 10-day TMA challenge. AD-like symptoms were assessed by ear thickening, scratching behavior, and pathological or immunofluorescence staining; Cytokines in the skin tissue and serum were measured by cytometric bead array; and the compositions of gut microbiota were assessed by 16S rRNA gene sequencing. AZI pretreatment accelerated the development of ear thickening and enhanced the severity of developed AD-like symptoms. AZI pretreatment promoted the infiltrations of neutrophil-like cells, T cells, and mast cells in ear skin. AZI pretreatment elevated the levels of IL-4, IL-6, and IL-17A in the ear skin of AD model mice, but it increased serum TNF-α and IL-6. AZI-pretreatment increased four gut bacterial genera (Bacteroides, Candidatus_Saccharibacteria_unclassified, Acetatifactor, Firmicutes_unclassified) but depleted three short-chain fatty acids producing gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). AD-associated symptoms were positively associated with skin IL-4 and IL-17A, serum TNF-α, and IL-6, and Acetatifactor, but they negatively correlated to the three decreased gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). Thus, our results demonstrate that AZI exposure deteriorates TMA-induced AD-like symptoms in mice, which is related to the imbalances of gut microbiota and skin/serum cytokines.

Background Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear. Methods In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition. Results The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM. Conclusions Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.

Background and aims Gut transit time is a key modulator of host–microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the ‘blue dye’ method as an inexpensive and scalable technique to measure transit time. Methods We assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study. Results We found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as Akkermansia muciniphila, Bacteroides spp and Alistipes spp (false discovery rate-adjusted p values

ObjectiveFrailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome.MethodsWe collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers.ResultsOlder adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman’s correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability.ConclusionsFrailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.

Despite that obesity is associated with many metabolic diseases, a significant proportion (10–30 %) of obese individuals is recognized as ‘metabolically healthy obeses’ (MHOs). The aim of the current study is to characterize the gut microbiome for MHOs as compared to ‘metabolically unhealthy obeses’ (MUOs). We compared the gut microbiome of 172 MHO and 138 MUO individuals from Chongqing (China) (inclined to eat red meat and food with a spicy taste), and performed validation with selected biomarkers in 40 MHOs and 33 MUOs from Quanzhou (China) (inclined to eat seafood and food with a light/bland taste). The genera Alistipes , Faecalibacterium and Odoribacter had increased abundance in both Chongqing and Quanzhou MHOs. We also observed different microbial functions in MUOs compared to MHOs, including an increased abundance of genes associated with glycan biosynthesis and metabolism. In addition, the microbial gene markers identified from the Chongqing cohort bear a moderate accuracy [AUC (area under the operating characteristic curve)=0.69] for classifying MHOs distinct from MUOs in the Quanzhou cohort. These findings indicate that gut microbiome is significantly distinct between MHOs and MUOs, implicating the potential of the gut microbiome in stratification and refined management of obesity.

The intestinal flora is recognized as a significant contributor to the immune system. In this research, the protective effects of oyster peptides on immune regulation and intestinal microbiota were investigated in mice treated with cyclophosphamide. The results showed that oyster peptides restored the indexes of thymus, spleen and liver, stimulated cytokines secretion and promoted the relative mRNA levels of Th1/Th2 cytokines (IL-2, IFN-γ, IL-4 and IL-10). The mRNA levels of Occludin, Claudin-1, ZO-1, and Mucin-2 were up-regulated, and the NF-κB signaling pathway was also activated after oyster peptides administration. Furthermore, oyster peptides treatment reduced the proportion of Firmicutes/Bacteroidetes, increased the relative abundance of Alistipes, Lactobacillus, Rikenell and the content of short-chain fatty acids, and reversed the composition of intestinal microflora similar to that of normal mice. In conclusion, oyster peptides effectively ameliorated cyclophosphamide-induced intestinal damage and modified gut microbiota structure in mice, and might be utilized as a beneficial ingredient in functional foods for immune regulation.

Chronic stress and the gut microbiota appear to comprise a feed-forward loop, which contributes to the development of depressive disorders. Evidence suggests that memory can also be impaired by either chronic stress or microbiota imbalance. However, it remains to be established whether these could be a part of an integrated loop model and be responsible for memory impairments. To shed light on this, we used a two-pronged approach in Japanese quail: first stress-induced alterations in gut microbiota were characterized, then we tested whether this altered microbiota could affect brain and memory function when transferred to a germ-free host. The cecal microbiota of chronically stressed quails was found to be significantly different from that of unstressed individuals with lower α and β diversities and increased Bacteroidetes abundance largely represented by the Alistipes genus, a well-known stress target in rodents and humans. The transfer of this altered microbiota into germ-free quails decreased their spatial and cue-based memory abilities as previously demonstrated in the stressed donors. The recipients also displayed increased anxiety-like behavior, reduced basal plasma corticosterone levels and differential gene expression in the brain. Furthermore, cecal microbiota transfer from a chronically stressed individual was sufficient to mimic the adverse impact of chronic stress on memory in recipient hosts and this action may be related to the Alistipes genus. Our results provide evidence of a feed-forward loop system linking the microbiota-gut-brain axis to stress and memory function and suggest that maintaining a healthy microbiota could help alleviate memory impairments linked to chronic stress. Availability of data and materials The datasets used during the current study are available from the corresponding author on reasonable request and they are available at https://doi.org/10.15454/JYITK4 .

Background Diet plays an important role in shaping the composition of gut microbiota. Starch is the main source of carbohydrates in diets of broilers. This study investigated the effects of dietary corn starch and resistant starch on composition and function of caecal microbiota of broilers. A total of 320, 1-day-old male Arbor Acres broiler chicks were randomly assigned into five groups including normal corn-soybean (NC) diet, corn starch (CS) diet group, 4%, 8% and 12% resistant starch (RS) diet groups. The caecal contents of 42-day old broilers were sampled and microbiota community was analysed with 16S rRNA gene sequences. Results The CS group increased the abundances of Bilophila, Eggerthella, Olsenella and Sellimonas and decreased proportion of Akkermansia, Eisenbergiella, Oscillospira, Ruminococcaceae NK4A214 group and Synergistes in the caecum of birds compared to the NC group. However, the birds from RS groups had higher abundances of Anaerofilum, Bacteroides, Desulfovibrio and Parasutterella and lower abundances of Alistipes, Bilophila, Christensenellaceae R-7 group, Eggerthella and Ruminiclostridium 1 than the CS group. Functional prediction of these changes in microbiota revealed that the CS diet drove caecal microbiota that were more inclined to utilize carbohydrates through glycolysis/gluconeogenesis metabolism, while the 8%RS and 12%RS diets depleted microbial glycolysis/gluconeogenesis and amino acids metabolism. Conclusion Dietary CS and RS alter the microbial composition and diversity, and modulate the metabolic pathways of microbial metabolism in caecum of broilers, which may further affect nutrient utilization and hindgut health of the host. © 2019 Society of Chemical Industry.

BACKGROUND: Despite tremendous interest in modulating the microbiome to improve health, the association between diet and the colonic mucosa–associated gut microbiome in healthy individuals has not been examined. OBJECTIVE: To investigate the associations between Healthy Eating Index (HEI)–2005 and the colonic mucosa–associated microbiota. METHODS: In this cross-sectional observational study, we analyzed bacterial community composition and structure using 16S rRNA gene (V4 region) sequencing of 97 colonic mucosal biopsies obtained endoscopically from different colon segments of 34 polyp-free participants. Dietary consumption was ascertained using an FFQ. Differences in α- and β-diversity and taxonomic relative abundances between the higher and lower score of total HEI and its components were compared, followed by multivariable analyses. RESULTS: The structure of the microbiota significantly differed by the scores for total HEI, total and whole fruits (HEI 1 and HEI 2), whole grains (HEI 6), milk products and soy beverages (HEI 7), and solid fat, alcohol, and added sugar (HEI 12). A lower score for total HEI and HEIs 2, 7, and 12 was associated with significantly lower richness. A lower score for total HEI was associated with significantly reduced relative abundance of Parabacteroides, Roseburia, and Subdoligranulum but higher Fusobacterium. A lower score for HEI 2 was associated with lower Roseburia but higher Bacteroides. A lower score for HEI 7 was associated with lower Faecalibacterium and Fusobacterium but higher Bacteroides. A lower score for HEI 12 was associated with lower Subdoligranulum but higher Escherichia and Fusobacterium (false discovery rate–adjusted P values

The grains that form the basis of most commercial chicken diets are rich in cellulose, an unbranched β-1,4-linked D-glucopyranose polymer, used as a structural molecule in plants. Although it is a predominant polysaccharide in cereal hulls, it is considered an inert non-fermentable fiber. The aim of the current study was to analyze the effect of in-feed supplementation of cellulose on the gut microbiota composition of broilers. Administration of cellulose to chickens, on top of a wheat-based diet, changed the caecal microbiota composition, as determined using pyrosequencing of the 16S rRNA gene. At day 26, a significantly (P < 0.01) higher relative abundance of the Alistipes genus was observed in the caeca of broilers fed the cellulose-supplemented diet, compared to animals fed the control diet. An in vitro batch fermentation assay showed a significant (P < 0.01) growth stimulation of Alistipes finegoldii in the presence of cellulose. In conclusion, in-feed supplementation of cellulose alters the microbiota composition at the level of the phylum Bacteroidetes, specifically the Alistipes genus. This suggests that cellulose is not essentially inert but can alter the gut micro-environment.

Tea polyphenols (TP) possess the ability to regulate dyslipidemia and gut microbiota dysbiosis. However, the underlying mechanism is still elusive. The present study explored the intervention of TP on high fat diet induced metabolic disorders, gut microbiota dysbiosis in mice, and the underlying intestinal mechanism. As a result, TP significantly ameliorated hyperlipidemia, improved the expression levels of hepatic lipid metabolism genes, and modulated gut microbiota. The underlying mechanism was supposed to rely on the maintaining of intestinal redox state by TP. Intestinal redox related indicators were significantly correlated with the distribution of gut microbiota. An unidentified genus of Lachnospiraceae, Bacteroides, Alistipes, and Faecalibaculum were identified as the biomarkers for intestinal redox state. Importantly, different dosages of TP modulated intestinal redox state and gut microbiota in varied patterns, and an overdose intake attenuated the beneficial effects on gut health. Our findings offered novel insights into the mechanism of TP on intestinal homeostasis.

Accumulative evidence has suggested that tea consumption has benefits in reducing body fat and alleviating metabolic syndrome. We hypothesize that benefits of tea consumption can be partially mediated by modulating intestinal microbiota via inhibiting the formation of lipopolysaccharides (LPS) and promoting the production of short chain fatty acids (SCFAs). C57BL/6J mice were fed a high fat diet with the addition of 1% water extracts of green tea, oolong tea and black tea. Results showed that the dietary supplementation of three tea water extracts equally improved the glucose tolerance and reduced a high fat diet-induced gain in weight, hepatic lipids, and white adipose tissue weights. This was accompanied by a significant reduction in plasma LPS and a significant increase in the production of SCFAs. The metagenomic analyses showed that the tea extracts changed the overall composition of gut microbiota and decreased the relative abundance of family Rikenellaceae and Desulfovibrionaceae. In addition, tea water extracts could also change the abundance of key operational taxonomic units (OTUs) including OTU473 (Alistipes), OTU229 (Rikenella), OTU179 (Ruminiclostridium) and OTU264 (Acetatifactor). In conclusion, three tea extracts could improve the glucose tolerance, induce the production of SCFAs and inhibit the production of endotoxin LPS, most likely mediated by modulating gut microbiota.

Sepsis is a common and often treacherous medical emergency with a high mortality and long-term complications in survivors. Though antibiotic therapy can reduce death rate of sepsis significantly, it impairs gut microbiota (GM), which play imperative roles in human health. In this study, we compared the therapeutic effects of antibiotics, probiotics, and Chinese medicine QRD on the survival rates of septic model and observed the GM characteristics of experimental rats via 16S rRNA gene amplicon sequencing. The 72 h survival rates of septic rat demonstrated the significant therapeutic effects in the three groups treated with antibiotics (AT), Chinses medicine QRD (QT), and probiotics (PT), which were elevated from the survival rate of 26.67% for the sepsis control group (ST) to 100.0% for AT, 88.24% for QT, and 58.33% for PT. The original characteristics of GM identified in the sham operation controls (SC) were relatively similar to those in PT and QT; nevertheless, the AT rats were shown dramatically decreased in the GM diversity. In addition, the septic rats in AT were revealed the higher abundances of Escherichia Shigella, Proteus, Morganella, Enterococcus, and Lysinibacillus, but the lower those of Parabacteroides, Alistipes, Desulfovibrio, Bacteroides, Helicobacter, Mucispirillum, Oscillibacter, Lachnospiraceae, and Ruminiclostridium 9, when compared to the PT and QT rats. By contrast, the GM of PT and QT rats shared similar diversity and structure. Our findings indicated that QRD increased the survival rates without impairment of the GM characteristics, which provides novel insights into the role of Chinese medicine in therapy and long-term recovery of sepsis.

Due to the different rates of diabetes in different ethnic groups and the structural differences in intestinal microbiota, this study evaluated the changes in diabetes-related intestinal microbiota in two ethnic groups. Fifty-six stool samples were collected from subjects from the Han and Mongolian ethnic groups in China, including participants without diabetes (non-diabetic, ND) and with type 2 diabetes (T2D). The 16S rDNA gene V3 + V4 area was extracted from microbiota, amplified by PCR, and used to perform high-throughput sequencing and screen differential microbiota associated with ethnicity. The results showed that there were 44 T2D-related bacterial markers in the Han subjects, of which Flavonifractor, Alistipes, Prevotella, Oscillibacter, Clostridium XlVa, and Lachnospiracea_incertae_sedis were most closely related to diabetes. There were 20 T2D-related bacterial markers in the Mongolian subjects, of which Fastidiosipila and Barnesiella were most closely related to diabetes. The common markers of T2D bacteria in the two ethnic groups were Papillibacter and Bifidobacterium. There were 17 metabolic pathways with significant differences between the ND and T2D groups in the Han group, and 29 metabolic pathways in the Mongolian group. The glutamatergic metabolic pathway was the only common metabolic pathway in two ethnic groups. The composition and function of diabetes-related bacteria were significantly different among the different ethnic groups, which suggested that the influence of ethnic differences should be fully considered when studying the association between diabetes and bacteria. In addition, the common bacterial markers found in diabetic patients of different ethnic groups in this study can be used as potential targets to study the pathogenesis and treatment of diabetes.

Recently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell α-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81 years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age > 70 years old) was significantly lower than the middle-aged group (age ≤ 70 years old). Furthermore, individual age was negatively correlated with HD5 concentration (r = − 0.307, p Collinsella, Alistipes, Peptococcaceae; unassigned, Lactobacillus, Lactococcus, Weissella, Christensenellaceae R-7 group, Megasphaera, and [Eubacterium] eligens group was significantly higher, and Lachnospiraceae; unassigned, Blautia, Anaerostipes, Fusicatenibacter, Dorea, and Faecalibacterium was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with Alistipes, Peptococcaceae; unassigned, and Christensenellaceae R-7 group and positively correlated with Lachnospiraceae; unassigned and Dorea. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.

Previous studies have reported lower fecal bacterial diversity in urban populations compared with those living in rural settings. However, most of these studies compare geographically distant populations from different countries and even continents. The extent of differences in the gut microbiome in adjacent rural versus urban populations, and the role of such differences, if any, during enteric infections remain poorly understood. To provide new insights into these issues, we sampled the gut microbiome of young children with and without acute diarrheal disease (ADD) living in rural and urban areas in northern Ecuador. Shotgun metagenomic analyses of non-ADD samples revealed small but significant differences in the abundance of microbial taxa, including a greater abundance of Prevotella and a lower abundance of Bacteroides and Alistipes in rural populations. Greater and more significant shifts in taxon abundance, metabolic pathway abundance, and diversity were observed between ADD and non-ADD status when comparing urban to rural sites (Welch’s t-test, P < 0.05). Collectively our data show substantial functional, diversity, and taxonomic shifts in the gut microbiome of urban populations with ADD, supporting the idea that the microbiome of rural populations may be more resilient to ADD episodes.

Obesity has become a major public health problem in recent decades. More effective interventions may result from a better understanding of microbiota alterations caused by weight loss and diet. Our objectives were (a) to calculate the fiber composition of a specially designed low‐calorie weight loss diet (WLD), and (b) to evaluate changes in the composition of gut microbiota and improvements in health characteristics during WLD. A total of 19 overweight/obese participants were assigned to 20%–40% reduced calories low‐carbohydrate high‐fat diet for four weeks. Protein and fat content in the composed diet was 1.5 times higher compared to that in the average diet of the normal weight reference group, while carbohydrate content was 2 times lower. Food consumption data were obtained from the assigned meals. Microbial composition was analyzed before and after WLD intervention from two sequential samples by 16S rRNA gene sequencing. During WLD, body mass index (BMI) was reduced on average 2.5 ± 0.6 kg/m2 and stool frequency was normalized. The assigned diet induced significant changes in fecal microbiota. The abundance of bile‐resistant bacteria (Alistipes, Odoribacter splanchnicus), Ruminococcus bicirculans, Butyricimonas, and Enterobacteriaceae increased. Importantly, abundance of bacteria often associated with inflammation such as Collinsella and Dorea decreased in parallel with a decrease in BMI. Also, we observed a reduction in bifidobacteria, which can be attributed to the relatively low consumption of grains. In conclusion, weight loss results in significant alteration of the microbial community structure., Our weight loss diet stimulated the growth of bile‐resistant fecal bacteria and reduced the levels of bacteria associated with inflammation. The appointed dietary regime introduced significant changes in the fecal microbiota of the test group compared to reference group levels. A high intake of vegetables and a low intake of cereals lead to high cellulose and pectin content in the diet and normalized the stool form.

This study aimed to investigate the beneficial effect of konjac oligosaccharides (KOS) on bone health in calcium-deficient mice. During the experimental period, low-calcium diet-fed mice were administered with calcium chloride to simulate daily calcium supplementation. Meanwhile, different levels of KOS intervened by adding them into the diet. After 8 weeks, the calcium balance status, bone mass parameters, and gut environment modulation were evaluated. The results showed that dietary KOS intervention alleviated the negative calcium balance, significantly promoted the trabecular number and cortical thickness, and remarkably enhanced the skeletal mechanical strength. Moreover, Pearson's correlation analysis among significantly changed gut microbiota, gut metabolites, and relevant physiological indexes showed that the microbial genera of Lactobacillus, Bifidobacterium, Mucispirillum, Alistipes, and unidentified Clostridia and gut metabolites of kynurenine and testosterone were significantly associated with increased bone mass. These findings provided a new insight into the effect of prebiotics on bone health.

Background While aging is a potent risk factor of dry eye disease, age-related gut dysbiosis is associated with inflammation and chronic geriatric diseases. Emerging evidence have demonstrated that gut dysbiosis contributes to the pathophysiology or exacerbation of ocular diseases including dry eye disease. However, the relationship between aging-related changes in gut microbiota and dry eye disease has not been elucidated. In this pilot study, we investigated the association between aging-dependent microbiome changes and dry eye severity in C57BL/6 male mice. Results Eight-week-old (8 W, n = 15), one-year-old (1Y, n = 10), and two-year-old (2Y, n = 8) C57BL/6 male mice were used. Dry eye severity was assessed by corneal staining scores and tear secretion. Bacterial genomic 16 s rRNA from feces was analyzed. Main outcomes were microbiome compositional differences among the groups and their correlation to dry eye severity. In aged mice (1Y and 2Y), corneal staining increased and tear secretion decreased with statistical significance. Gut microbiome α-diversity was not different among the groups. However, β-diversity was significantly different among the groups. In univariate analysis, phylum Firmicutes, Proteobacteria, and Cyanobacteria, Firmicutes/Bacteroidetes ratio, and genus Alistipes, Bacteroides, Prevotella, Paraprevotella, and Helicobacter were significantly related to dry eye severity. After adjustment of age, multivariate analysis revealed phylum Proteobacteria, Firmicutes/Bacteroidetes ratio, and genus Lactobacillus, Alistipes, Prevotella, Paraprevotella, and Helicobacter to be significantly associated with dry eye severity. Conclusions Our pilot study suggests that aging-dependent changes in microbiome composition are related to severity of dry eye signs in C57BL/6 male mice.

ObjectivesGut dysbiosis is associated with chronic kidney disease (CKD), and serum free immunoglobulin light chains (FLCs) are biomarkers for CKD. This study aims to assess the CKD gut microbiome and to determine its impact on serum FLC levels.MethodsTo control for confounders, 100 patients and sex- and age-matched healthy controls (HCs) were recruited. The gut microbiome was assessed by sequencing 16S rRNA gene V3-V4 hypervariable regions. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was applied to infer functional metabolic pathways. When observing group differences in the microbiome and predicted metabolic pathways, demographic confounders were adjusted using binary logistic regression; when examining impacts of the gut microbiome and metabolic pathways on serum FLCs, factors influencing FLC levels were adjusted using multiple regression.ResultsPrincipal coordinate analysis revealed a significantly different bacterial community between the CKD and HC groups (P < 0.05). After adjusting for confounders, lower Chao 1, observed species and Shannon indices based on binary logistic regression predicted CKD prevalence. Actinobacteria, Alistipes, Bifidobacterium and Bifidobacterium longum enrichment, upregulation of metabolic pathways of bacterial toxin, chloroalkane and chloroalkene degradation, and Staphylococcus aureus infection also predicted CKD prevalence (P < 0.05). Furthermore, depletion of Actinobacteria and Bifidobacterium and reduced chloroalkane and chloroalkene degradation predicted high levels of FLC λ (P < 0.05).ConclusionsGut dysbiosis in CKD patients was confirmed by controlling for confounders in the present study. Additionally, the association between gut dysbiosis and FLC λ levels demonstrates the existence of crosstalk between the microbiome and immune response in CKD.

Peptide YY (PYY), produced by endocrine L cells in the gut, is known for its critical role in regulating gastrointestinal functions as well as satiety. However, how these processes are integrated with maintaining a healthy gut microbiome composition is unknown. Here, we show that lack of PYY in mice leads to distinct changes in gut microbiome composition that are diet‐dependent. While under chow diet only slight differences in gut microbiome composition could be observed, high‐fat diet (HFD) aggravated these differences. Specifically an increased abundance of the Bacteroidetes phylum with a corresponding decrease of the Firmicutes/Bacteroidetes ratio could be detected in Pyy‐knockout (KO) mice in response to HFD. Detailed analysis of the Bacteroidetes phylum further revealed that the Alistipes genus belonging to the Rikenellaceae family, the Parabacteroides belonging to the Tannerellaceae family, as well as Muribaculum were increased in Pyy‐KO mice. In order to investigate whether these changes are associated with changed markers of gut barrier and immunity, we analyzed the colonic expression of various pro‐inflammatory cytokines, as well as tight junction proteins and mucin 2, and identified increased mRNA expression of the tight junction proteins Cldn2 and Ocel1 in Pyy‐KO mice, while pro‐inflammatory cytokine expression was not significantly altered. Together these results highlight a critical gene‐environment interaction between diet and the gut microbiome and its impact on homeostasis of the intestinal epithelium under conditions of reduced PYY signaling which is commonly seen under obese conditions.