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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.

Glucagon-like peptide-1 (GLP-1) reduces postprandial hyperglycaemia, but its short half-life inhibits clinical application. The aim of the current study was to evaluate the treatment efforts of an engineered strain, Lactobacillus plantarum-pMG36e-GLP-1 (L. plantarum-pMG36e-GLP-1), that continuously expresses GLP-1 in spontaneous type 2 diabetes mellitus (T2DM) monkeys. After 7 weeks of oral supplementation with L. plantarum-pMG36e-GLP-1, the fasting blood glucose (FPG) of monkeys was significantly (p

The microbiome in gastrointestinal tracts play an important role in regulating nutrient utilization and absorption, gut immune function, and host growth or development. This study was conducted to investigate the composition and dynamic distribution of caecal microbiota in pullets during the first 16 weeks. Growth performance, immune organs index, and intestinal morphology of pullets were analyzed at 3, 6, 12 and 16 weeks of age. The caecal contents were collected for microbiota analysis by 16S rRNA gene sequencing method. With advancing ages in pullets, the gradually increased average daily feed intake (ADFI), feed conversion ratio (FCR) and intestinal villus height, but the gradually decreased organs index of thymus and bursa were determined. Meanwhile, more abundant caecal bacterial communities were determined from pullets at 12 and 16 weeks of age than those at 3 and 6 weeks of age. Furthermore, the dominant microflora of pullets from different weeks of age were analyzed by using LEfSe: The higher abundance of Blautia, Prevotella, Alistipes, and Eggerthella were found at 6 weeks; Anaerostipes, Oscillospira, Enterococcus and Methanobrevibacter were determined at 12 weeks; and the higher abundance of Parabacteroides, Anaerofustis, Lactobacillus and Butyricimonas were determined at 16 weeks. Further functional predicted analysis by PICRUSt revealed that the endocrine system and carbohydrate metabolism were significantly developed at 3 weeks. The development of the immune system was predicted to be mainly during 6 to 12 weeks, while cardiovascular diseases and circulatory system were during 12 to 16 weeks. In addition, the significantly negative correlation between Bacteroides and villus height, the significantly negative correlation between growth parameters (ADFI and FCR) and Bacteroides, Oscillospira and Alistipes; and the significantly positive relations between growth parameters (ADFI and FCR) and Bilophila, Lactobacillus, Rikenella and Anaerofustis were determined by using Pearson analyses. In conclusion, our data demonstrated that growth performance and intestinal morphology correlate well with caecal microbiota, which could provide new insights to establish or develop nutritional strategies to manage the intestinal health or development of laying pullets.

Alzheimer's disease (AD) is a neurodegenerative disease that remarkably imposes a huge global public health burden. Yeast β-glucans have been incorporated in functional foods and used in prophylactic applications owing to their biological effects. However, few studies had investigated the effects of yeast β-glucans on neurodegenerative diseases. Here, gut microbiota and metabolites SCFAs were analyzed through high-throughput 16S rRNA gene sequencing and GC-MS, respectively. Results indicated that yeast β-glucans could prominently shape the intestinal flora and produce SCFAs. Aβ1-42-induced AD mice treated with small-molecular yeast β-glucan (S-β-Glu) or macro-molecular yeast β-glucan (M-β-Glu) exhibited evident alterations of the composition of the gut microbiota, especially in some beneficial bacteria and inflammatory-related bacteria such as Lactobacillus, Bifidobacterium, Desulfovibrio, Oscillibacter, Mucispirillum, Alistipes, Anaerotruncus, and Rikenella. M-β-Glu regulated gut microbiota act as prebiotics better than S-β-Glu. Correlation analysis demonstrated the key microbiota closely associated with AD-related pathologies and cognition. Moreover, M-β-Glu and S-β-Glu ameliorated neuroinflammation and brain insulin resistance (IR), which played a central role in the process of AD pathology. This study broadened the underlying applications of yeast β-glucans as a novel dietary supplementation to prevent early-stage pathologies associated with AD by regulating gut microbiota and the potential mechanism might be ameliorating brain IR.

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.

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.

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.

This study aimed to investigate the effects of polysaccharide peptides from Ganoderma lucidum (GLPP) on hyperlipidaemia and gut microbiota dysbiosis in high-fat diet (HFD)-exacerbated hypercholesterolemic rats. Results showed that oral administrations of GLPP markedly alleviated the dyslipidaemia through decreasing the serum levels of triglyceride (TG), cholesterol (TC), free fatty acids (FFA) and low-density lipoprotein cholesterol (LDL-C), and significantly suppressing hepatic lipid accumulation and steatosis. Metagenomic analysis revealed that GLPP supplementation produced significant structure changes on the intestinal microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. The Spearman's correlation analysis revealed that the serum and hepatic lipid profiles were negatively correlated with Jeotgalicoccus, Ignavigranum, Sporosarcina, Bacteroides, Anaerovorax, Parasutterella, Alistipes and Alloprevotella, but positively correlated with Allobaculum, Phascolarctobacterium, Psychrobacter, Enterorhabdus, Blautia and Roseburia. Meanwhile, the GLPP treatment regulated the mRNA expression responsible for hepatic lipid metabolism and promoted fecal excretion of total bile acids (BAs). These findings indicated that GLPP ameliorate lipid metabolic disorders through modulating gut microbiota structure and regulating the genes involved in hepatic lipid and cholesterol metabolism.

Gut microbiota and amino acids that are one of their metabolites play important roles in the mechanism of pathology of Parkinson's disease (PD). It has been reported that the level of amino acids in vivo participate in neurodegeneration by regulating adaptive immune response, while the current researches on alteration of amino acids in gut microbiota are still insufficient. We hypothesized that alterations in gut microbiota might be accompanied by altered concentrations of amino acids, leading to the occurrence of PD. In this study, we collected stool samples from PD and healthy controls to analyse fecal microbiome and targeted metabolome by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography coupled to mass spectrometry (GC-MS). At the genus level, there was a greater abundance of Alistipes, Rikenellaceae_RC9_gut_group, Bifidobacterium, Parabacteroides, while Faecalibacterium was decreased in fecal samples from PD patients. Moreover, fecal branched chain amino acids (BCAAs) and aromatic amino acids concentrations were significantly reduced in PD patients compared to controls. Our study not only finds the abundance of certain gut microbiota in PD,but also reveals that it is related to BCAAs and aromatic amino acids. These findings are beneficial to identifying new therapeutic targets for PD by regulating diet and/or gut microbiota.

Untreated insomnia can harm physical and psychological health, ultimately affecting quality of life. This study aims to explore the beneficial effects of queen bee larva freeze-dried powder (QBLF) on p-chlorophenylalanine (PCPA)-induced insomnia and related neurotransmitter disorders and determine whether this improvement is related to the gut microbiota. The results showed that the γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) levels in the hypothalamus and serum were significantly decreased in the PCPA-induced insomnia group compared with the control group. QBLF treatment improved insomnia symptoms and significantly regulated GABA and 5-HT levels. Furthermore, QBLF modulated the gut microbiota composition and reversed insomnia-induced gut microbiota alterations, such as reduced relative abundances of Desulfovibrio, Alistipes and Lachnospiraceae sp. NK4A136. Specifically, the relative abundance of Lactobacillus was significantly increased. Lactobacillus was positively correlated with insomnia-related neurotransmitter concentrations. Desulfovibrio, Alistipes and Lachnospiraceae sp. NK4A136 showed an opposite trend. Moreover, predictive function analysis revealed that QBLF modulated dysfunction due to PCPA-induced insomnia, such as significantly reduced gene expression related to the metabolism of cofactors and vitamins. Therefore, QBLF can ameliorate PCPA-induced insomnia and insomnia-related neurotransmitter disorders. Furthermore, the insomnia ameliorating effect of QBLF may relate to the regulation of the composition and structure of the gut microbiota in insomniac mice.

Bovine colostrum samples were collected from 9 healthy cows at 4 time points (0, 1, 2, and 6 d after calving) at a dairy farm in Ningxia, China, and the bacterial diversity was explored using 16S rRNA pyrosequencing. Colostrum samples were dominated by phyla of Firmicutes, Bacteroides, Proteobacteria, and Actinobacteria with 35 predominant genera, including Lactobacillus, Bacteroides, Escherichia_Shigella, Collinsella, Klebsiella, Alistipes, Clostridium_sensu_stricto_1, Prevotella_9, and Bifidobacterium. The core microbiota of bovine colostrum contained 58 genera and 5 species. The alpha and beta diversity analysis indicated bovine colostrum microbiota was stable at the first 3 days but changed at 6 d. At 6 d, the relative abundance of most predominant genera decreased, while Escherichia_Shigella, Acinetobacter, Lactococcus, and Streptococcus increased.

Oral exposure to toxic metals such as cadmium (Cd), lead (Pb), copper (Cu) and aluminum (Al) can induce various adverse health effects in humans and animals. However, the effects of these metals on the gut microbiota have received limited attention. The present study demonstrated that long-term toxic metal exposure altered the intestinal microbiota of mice in a metal-specific and time-dependent manner. Subchronic oral Cu exposure for eight weeks caused a profound decline in gut microbial diversity in mice, whereas no significant changes were observed in groups treated with other metals. Cd exposure significantly increased the relative abundances of organisms from the genera Alistipes and Odoribacter and caused marked decreases in Mollicutes and unclassified Ruminococcaceae. Pb exposure significantly decreased the abundances of eight genera: unclassified and uncultured Ruminococcaceae, unclassified Lachnospiraceae, Ruminiclostridium_9, Rikenellaceae_RC9_gut_group, Oscillibacter, Anaerotruncus and Lachnoclostridium. Cu exposure affected abundances of the genera Alistipes, Bacteroides, Ruminococcaceae_UCG-014, Allobaculum, Mollicutes_RF9_norank, Rikenellaceae_RC9_gut_group, Ruminococcaceae_unclassified and Turicibacter. Al exposure increased the abundance of Odoribacter and decreased that of Anaerotruncus. Exposure to any metal for eight weeks significantly decreased the abundance of Akkermansia. These results provide a new understanding regarding the role of toxic metals in the pathogenesis of intestinal and systemic disorders in the host within the gut microbiota framework.

To determine whether voluntary wheel running could improve cognitive function from both the young and middle-aged APP/PS1 mice and the underlying mechanisms involved in. Young (9-weeks old) and middle-aged (24-weeks old) APP/PS1 mice were randomly assigned into control and exercise groups, respectively. Mice from exercise group had free and unlimited access to the running wheel for a total of 16 weeks. Voluntary exercise only improved cognitive function from young but not the middle-aged APP/PS1 mice. This might be owing to that in young APP/PS1 mice voluntary exercise reduced tau phosphorylation via inhibiting p-GSK3β activity, as well as reduced neuro-inflammation and elevated key proteins involved in synaptic plasticity. Additionally, exercise also elevated circulating L-Valine, Glucosamine, Formylanthranilic acid, Myristic acid level and improved gut microbiota profiles (i.e. elevated Oscillibacter, EF097061_g, EU454870_g, EU504554_g, EU505046_g and EF096172_g and reduced Alistipes). Improved circulating metabolites and intestinal microbiome might also contribute to improved learning and memory abilities post exercise. For the middle-aged APP/PS1 mice, exercise reduced ADAM10 and GFAP protein expression in hippocampus, with no notable alterations in circulating metabolites; additionally, mice from exercise group had markedly reduced abundance of the phyla Proteobacteria and Tenericutes, genera Bacteroides and Faecalibacterium, and elevated abundance of the genera Allobaculum. It is suggested that voluntary exercise should be initiated at an early adulthood period rather than at late stage in order to prevent cognitive decline or Alzheimer's disease.

Gamma-amino butyric acid (GABA) is an active biogenic substance synthesized in plants, fungi, vertebrate animals and bacteria. Lactic acid bacteria are considered the main producers of GABA among bacteria. GABA-producing lactobacilli are isolated from food products such as cheese, yogurt, sourdough, etc. and are the source of bioactive properties assigned to those foods. The ability of human-derived lactobacilli and bifidobacteria to synthesize GABA remains poorly characterized. In this paper, we screened our collection of 135 human-derived Lactobacillus and Bifidobacterium strains for their ability to produce GABA from its precursor monosodium glutamate. Fifty eight strains were able to produce GABA. The most efficient GABA-producers were Bifidobacterium strains (up to 6 g/L). Time profiles of cell growth and GABA production as well as the influence of pyridoxal phosphate on GABA production were studied for L. plantarum 90sk, L. brevis 15f, B. adolescentis 150 and B. angulatum GT102. DNA of these strains was sequenced; the gadB and gadC genes were identified. The presence of these genes was analyzed in 14 metagenomes of healthy individuals. The genes were found in the following genera of bacteria: Bacteroidetes (Bacteroides, Parabacteroides, Alistipes, Odoribacter, Prevotella), Proteobacterium (Esherichia), Firmicutes (Enterococcus), Actinobacteria (Bifidobacterium). These data indicate that gad genes as well as the ability to produce GABA are widely distributed among lactobacilli and bifidobacteria (mainly in L. plantarum, L. brevis, B. adolescentis, B. angulatum, B. dentium) and other gut-derived bacterial species. Perhaps, GABA is involved in the interaction of gut microbiota with the macroorganism and the ability to synthesize GABA may be an important feature in the selection of bacterial strains – psychobiotics.

The gut microbiota of Mongolian hosts has distinctive characteristics due to their meat- and dairy-oriented daily diets and unique genotype. The aim of the present study was to investigate the effect of switching from the typical high protein and fat Mongolian diets to carbohydrate-rich meals composed principally of wheat, rice and naked oats on the host gut microbiota within 3 weeks. Our study took the advantage of the long sequence reads produced by the PacBio single molecule real-time sequencing technology to enable the profiling of subjects’ gut microbiota communities along the diet intervention to the species precision. We found that the bacterial richness and diversity decreased apparently along the diet intervention. During the diet intervention, the gut microbiota composition displayed no significant difference at phylum level (with major phyla of Firmicutes, Bacteroidetes, Tenericutes and Proteobacteria). The relative abundances of some genera such as Bacteroidetes, Faecalibacterium, Roseburia, Alistipes, Streptococcus, and Oscillospira were significantly altered after the diet switching started. Notably, significant changes were also observed in the proportions of the species Bacteroides dorei, Bacteroides fragilis, Bacteroides thetaiotaomicron, Ruminococcus albus, Ruminococcus faecis, Roseburia faecis and Eubacterium ventriosum. These results have demonstrated that diet and host gut microbiota is closely linked.

Aims Whether dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) animal models undergo self-healing remains unclear. Therefore, the study aim was to determine if these models have self-healing ability. Main methods UC was induced using 4% DSS in male KM mice. Histopathological and inflammatory cytokine were evaluated. Fecal samples were analyzed by 16S rDNA gene sequencing. Key findings Physiological and inflammatory cytokine changed obviously on days 4–14 of establishment and returned to normal levels by day 21. The degrees of inflammation and injury in pathological sections decreased within 14 days compared with those on day 7. Interleukin (IL)-17A, IL-6, and C-reactive protein (CRP) levels fluctuated daily and were highest at 10 AM, 11 AM, and 8 PM, respectively. Intestinal flora disturbance was most obvious on days 7 and 14. The abundances of Lactobacillus and Alistipes decreased, whereas those of Streptococcus, Escherichia–Shigella, and Oscillibacter increased and mostly recovered by day 21. Lactobacillus and serum CRP level were negatively correlated with inflammation, whereas Streptococcus and Escherichia–Shigella were positively correlated with serum IL-6 level. Significance The DSS-induced UC murine model was shown to undergo self-healing. Intestinal flora disturbance in the model were obvious from days 4 to 14 and had mostly recovered by day 21.

Alistipes spp is a genus of Gram-negative anaerobic rods involved in very few human diseases. We report the first case of abdominal infection due to Alistipes onderdonkii in a 58-year-old man with a history of chronic obstructive pulmonary disease. He presented with abdominal pain and general malaise after retrogastric drainage for a pancreatitis episode a few days earlier. After the diagnosis of diffuse peritonitis with perforation and necrotizing pancreatic collection, abundant pancreatic fluid was drained and yielded the isolation of A. onderdonkii in pure culture. Resistance to penicillin and moxifloxacin was documented for this strain. Treatment with metronidazole was prescribed, and the patient was discharged after improvement of his general condition.

T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy associated with unfavorable factors including male gender and over nine years of age. Chemotherapy toxicity continues to present a major challenge. There is a need to develop novel natural agents to improve survival and quality of life in patients with T-ALL. 20(S)-ginsenoside Rh2 (GRh2) exhibits immune regulation and anti-tumor effects in both cellular and murine xenograft models. In the present study, the anti-cancer mechanisms of 20(S)-GRh2 involved in the immune system and intestinal microbiota were investigated in T-ALL mice. We revealed that 20(S)-Rh2 suppressed T-ALL by blocking the PI3K/Akt/mTOR signaling pathway, and enhanced immunity in the spleen by regulating immune factors. In addition, 20(S)-GRh2 altered the composition of the gut microbiota, and promoted intestinal homeostasis by elevating the levels of tight junction proteins, antimicrobial peptides and IgA. 20(S)-GRh2 ameliorated the LPS-induced inflammatory response in the intestine of T-ALL mice. Furthermore, Bacteroidetes, Verrucomicrobia, Akkermansia, Lactobacillus, and Lachnospiraceae_NK4A136_group were positively correlated with anti-tumor immune factors, intestinal barrier-related factors, and the anti-inflammatory response. Conversely, Firmicutes, Proteobacteria, Parabacteroides and Alistipes had the opposite correlation. Collectively, these results suggest that 20(S)-GRh2 is a safe and effective natural product, that shows promise for the prevention and treatment of T-ALL.

Milk, which contains β-lactoglobulin (β-Lg; a major allergenic protein), is the most common food allergen and one of the earliest discovered. Human milk oligosaccharides (HMOs), especially 2′-fucosyllactose (2′-FL), have multiple effects as prebiotics, including improvements to immune regulation, gut health, and cognition. In this study, we investigated the effects of HMOs on immunoregulation and intestinal flora in a β-Lg-induced milk allergy mouse model. HMOs supplementation reduced allergic symptoms, decreased serum IgE and β-Lg-specific IgE, and significantly increased levels of the anti-inflammatory cytokines IL-10, TGF-β, and IFN-γ compared to those in the β-Lg allergy group. Furthermore, HMOs and 2′-FL interventions improved richness and diversity of fecal microbiota. The relative abundance of Lactobacillus significantly increased, while that of Lactococcus and Alistipes significantly decreased. In summary, our study shows that HMOs and 2′-FL supplementation relieved β-Lg-induced allergies.

The incidence of type 1 diabetes mellitus (T1DM) is increasing year by year, gut microbiota is considered to be closely related to the occurrence and development of T1DM in recent years. In this study, Sprague Dawley (SD) rats were intraperitoneally injected with 75mg/kg streptozotocin to establish T1DM model, fecal samples were collected and DNA were extracted, 16S rRNA microbial gene clone library were constructed, and lastly high-throughput sequencing and bioinformatics analysis were performed. The results showed that the abundances of pathogenic bacteria such as Ruminococcaceae, Shigella, Enterococcus, Streptococcus, Rothia and Alistipes associated with infection and inflammation in T1DM rats were up-regulated, while the abundances of beneficial bacteria such as Lactobacillus, Faecalitalea, Butyricicoccus and Allobaculum were reduced. Among them, Butyricicoccus and Allobaculum protect intestinal barrier function by producing short-chain fatty acids. This study suggests that intestinal inflammation and reduction of short chain fatty acids (SCFAs) caused by the imbalance of gut microbiota are crucial to the pathogenesis of T1DM.

In this study, Procambarus clarkii (P. clarkii) were exposed to different concentrations (0, 2, 5 and 10 mg/L) of cadmium (Cd). We studied the effects of Cd exposure on intestinal histology and microbiota in P. clarkii. The results demonstrated that exposure to Cd caused histological alterations in the intestines of P. clarkii. Meanwhile, high-throughput sequencing analysis revealed that Cd exposure could alter the richness, diversity, and composition of intestinal microbiota in P. clarkii. At the phylum level, the relative abundances of the prevalent phyla Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria changed significantly after exposure to Cd. At the genus level, the most prevalent genera with significant difference in relative abundance were Bacteroides, Clostridium XlVb, Hafnia, Buttiauxella, Shewanella, Anaerorhabdus, Alistipes, Arcobacter, Azoarcus, Chryseobacterium, and so on. Furthermore, functional prediction analysis of intestinal microbial communities showed that Cd exposure could significantly alter the pathways related to metabolism, diseases, cellular processes, and so on. Taken together, exposure to Cd could induce intestinal histological damage and affect intestinal microbiota composition and functions of P. clarkii. Our study can be an important step toward a better understanding of the toxic effects of Cd on aquatic crustaceans.

Undernutrition remains one of the key global health challenges facing children today. Distinct microbial profiles have been associated with obesity and undernutrition, although mechanisms behind these associations are unknown. We sought to understand how protein–energy undernutrition alters the microbiome and to propose mechanisms by which these alterations influence the malnourished phenotype. Outbred CD1 neonatal mice were undernourished by timed separation from lactating dams, while control animals nursed ad libitum . 16S rRNA gene sequencing and compositional analysis identified microbes from luminal contents of ileum, cecum and colon, while whole metagenome shotgun sequencing identified microbial gene content. Our results suggest that the most important determinant of microbiome composition is body compartment; communities derived from ileum are distinct from those from cecum and colon as observed by phylogenetic clustering analysis. However, within each compartment, microbiota from undernourished and control mice cluster separately. At the phylum level, undernourished mice harbor more Verrucomicrobia and less Bacteroidetes in the distal intestine; these changes are driven by an increase in Akkermansia muciniphila and decreases in Bacteroides and Alistipes . Undernourished mice have an overall loss of microbial community richness and diversity and are deficient in multiple microbial genetic pathways including N -glycan, inositol phosphate and one-carbon metabolism. Losses in these microbial genes may confer less efficient extraction of energy from nondigestible dietary components including glycans and phytates, whereas epigenetic alterations provide a means of persistently altering metabolism even after adequate nutrition is restored. Thus, the microbiome of an undernourished host may perpetuate states of poor nutrition via multiple mechanisms.

The mammalian gastrointestinal tract harbors a highly complex microbial community that comprises hundreds of different types of bacterial cells. The gastrointestinal microbiota plays an important role in the function of the host intestine. Most cancer patients undergoing pelvic irradiation experience side effects such as diarrhea; however, little is currently known about the effects of irradiation on the microorganisms colonizing the mucosal surfaces of the gastrointestinal tract. The aim of this study was to investigate the effects of gamma irradiation on the compositions of the large and small intestinal microbiotas. The gut microbiotas in control mice and mice receiving irradiation treatment were characterized by high-throughput sequencing of the bacterial 16S rRNA gene. Irradiation treatment induced significant alterations in the bacterial compositions of the large and small intestines at the genus level. Unexpectedly, irradiation treatment increased the number of operational taxonomic units in the small intestine but not the large intestine. In particular, irradiation treatment increased the level of the genera Alistipes in the large intestine and increased the level of the genus Corynebacterium in the small intestine. By contrast, compared with that in the corresponding control group, the level of the genera Prevotella was lower in the irradiated large intestine, and the level of the genera Alistipes was lower in the irradiated small intestine. Overall, the data presented here reveal the potential microbiological effects of pelvic irradiation on the gastrointestinal tracts of cancer patients.

Cyclophosphamide (CP) is the most commonly used drug in autoimmune disease, cancer, blood and marrow transplantation. Recent data revealed that therapy efficacy of CP is gut microbiota-dependent. So, it is very important to understand how CP affects intestinal microbiota and immune function. In this study, the effects of CP on mice immuno-activity were firstly evaluated, then, the fecal microbiota from normal and CP-treated mice was compared, and the characteristic bacterial diversity and compositions were identified, using 454 pyrosequencing technology. The results showed that CP reduced the diversity and shifted the fecal microbiota composition. Specifically, CP treatment decreased the proportion of Bacteroidetes while increased the proportion of Firmictutes in the microbial community. Most importantly, specific microbiota signatures belonging to Bacteroides acidifaciens, Streptococcaceae and Alistipes were also identified, which would provide new insight into the efficacy and side effects in clinical usage of CP. This should be helpful for further demonstration of CP's action mechanism, development of personalized therapy strategies, and prediction of potential side effects related to various treatment regimens of CP.

Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders with evidence of genetic predisposition. Intestinal disturbances are reported in ASD patients and compositional changes in gut microbiota are described. However, the role of microbiota in brain disorders is poorly documented. Here, we used a murine model of ASD to investigate the relation between gut microbiota and autism-like behaviour. Using next generation sequencing technology, microbiota composition was investigated in mice in utero exposed to valproic acid (VPA). Moreover, levels of short chain fatty acids (SCFA) and lactic acid in caecal content were determined. Our data demonstrate a transgenerational impact of in utero VPA exposure on gut microbiota in the offspring. Prenatal VPA exposure affected operational taxonomic units (OTUs) assigned to genera within the main phyla of Bacteroidetes and Firmicutes and the order of Desulfovibrionales, corroborating human ASD studies. In addition, OTUs assigned to genera of Alistipes, Enterorhabdus, Mollicutes and Erysipelotrichalis were especially associated with male VPA-exposed offspring. The microbial differences of VPA in utero-exposed males deviated from those observed in females and was (i) positively associated with increased levels of caecal butyrate as well as ileal neutrophil infiltration and (ii) inversely associated with intestinal levels of serotonin and social behaviour scores. These findings show that autism-like behaviour and its intestinal phenotype is associated with altered microbial colonization and activity in a murine model for ASD, with preponderance in male offspring. These results open new avenues in the scientific trajectory of managing neurodevelopmental disorders by gut microbiome modulation.

Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.

Lead contamination is an environmental problem, especially in developing countries; due to the nondegradable characteristics of lead, it is easily deposited in human and animal bodies by the food chain. Probiotics are regarded as a good tool to remove lead ions in the intestine and maintain gut health conditions, but previous studies failed to elucidate the relationship among probiotics, the host and the gut microbiota. In the present study, B. coagulans R11 was employed as the “lead removal tool” in lead-exposed mouse, and the effects of B. coagulans R11 on intestinal cells, the microbiota and faecal microRNAs were tested. The results indicated that B. coagulans R11 had no negative effects on mouse intestine model cells and helped keep cells in a normal proliferation ratio and reduce the reactive oxygen species and apoptosis ratios under lead exposure conditions. An in vivo mouse experiment also showed that B. coagulans R11 feeding could reduce the intestinal villi damage caused by lead through adjusting the microbiota structure and function, such as increasing the genus abundance of Akkermansia and Alistipes, decreasing the genus abundance of Alloprevotella, Lachnospiraceae, Parabacteroides and Ruminiclostridium, and keeping the protein dltD existing. Host faecal microRNAs may be influenced by lead and B. coagulans R11, which may change the microbiota structure. Thus, B. coagulans R11 has the potential to be developed and considered as the probiotic that protects the host gut against villi damage and gut microbiota structure and function disorders during lead exposure.

Background The microbiota community is considered as an organ of the human body. Recent studies have found that dysbiosis may have an impact on the interaction between immune regulation and tumor treatment. The main objective of this study is to characterize the gut microbiota in patients with non-small cell lung cancer (NSCLC) in advanced stages, and its relationship with obesity, smoking habits, clinical pathological features and response to treatment with immune-checkpoints blockers (ICB). Methods 16S rRNA gene sequencing was performed on 48 stool samples from advanced NSCLC patients prior to treatment with ICB (PD-1 inhibitor and PD-L1 inhibitor). The database used for the taxonomic assignation was the SILVA_release_132. The parametric statistical analysis was performed in SPSS package (15.0). A p-value Results The average age of the 48 patients was (64±10 years), of which 36 patients were male, 27 patients present PD-L1 positive, 28 patients with smoking habits. 261 different genus were detected in all the samples, being Bacteroides 28.11%, Alistipes 6.58% and Prevotella 4.67% the more frequently found. Non-smokers presented significantly higher richness and diversity (Chao1 p = 0.001, Shannon p = 0.001, Simpson p = 0.03) compared with current and former smokers. Greater abundance of genus Blautia was associated with obesity (p = 0.043). In addition, according to histology, greater abundance of genus Odoribacter was observed in squamous cell carcinoma patients compared to adenocarcinoma (p = 0.04); and regarding stage, stage IIIB patients presented higher proportion of genus Lactobacillus than stage IV (p = 0.017).Patients with progression disease to the ICB treatment presented significantly higher abundance of genus Ruminococcaceae_UCG-013 (p = 0.019). Conclusions We have been demonstrated a potential relationship between the gut microbiota in NSCLC patients and clinical-pathological features, which requires confirmation in a larger study. The more relationship with the ICB is under evaluation and will be presented at the meeting. Funded by CB16/12/00350 from CIBEROnc, PI18/00226, and PI15-00753 from ISCIII. Legal entity responsible for the study Fundacion Investigacion Hospital General Universitario Valencia. Funding CIBEROnc, Instituto de Salud Carlos III. Disclosure All authors have declared no conflicts of interest.

The effects of wheat bran feruloylated oligosaccharides (FOs) on the gut microbiota were studied. Furthermore, xylo-oligosaccharides (XOs) and ferulic acid (FA) as the two major moieties were used to demonstrate the structural influence of FOs on microbiota modulation effects. FOs promoted the phylum Firmicutes and Actinobacteria and decreased the relative abundance of Bacteroidetes and Proteobacteria. FA significantly increased the phylum Bacteroidetes. At the genus level, FOs promoted beneficial microorganism such as Bifidobacterium and Faecalibacterium, and inhibit the growth of disease-related bacteria such as Alistipes, Bilophila, Dorea, Enterobacteriaceae, and Oscillopira. FA significantly increased Bacteroides, Dialister and decreased Coprococcus, Enterobacteriaceae, Megamonas, Oscillospira. In terms of metabolites, FOs and XOs increased the content of short-chain fatty acids (SCFAs) but inhibited the production of branched-chain fatty acids (BCFAs). However, FA inhibited the production of both SCFAs and BCFAs. In conclusion, wheat bran FOs showed the prebiotic effects and further promoted the production of SCFAs due to the combined actions of oligosaccharides and FA moieties. Our findings highlighted that composition and structure should be taken into consideration for selecting FOs as prebiotics.

Background The gut microbiota plays a key role in the maintenance of human health and mediates the beneficial effects of natural products including polyphenols. Previous studies have demonstrated that the polyphenol-rich Pandanus tectorius fruit extract (PTF) was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia, and polyphenols can significantly change the structure of the gut microbiota. Purpose: In this study, we assessed whether the modulation of the gut microbiota plays a key role in the PTF-induced anti-hyperlipidaemic effects. Methods Male C57BL/6 J mice were induced with hyperlipidaemia by consuming a high-fat diet (HFD) for 4 weeks. Then, the mice were orally administered PTF, antibiotics (ampicillin+ norfloxacin), PTF+antibiotics or vehicle for another 6 weeks. Body weights and 24-h food intake were assessed weekly. At the end of the experiment, fresh stools were collected for 16S RNA pyrosequencing, and blood and liver and fat tissue were collected for pharmacological analysis. Results PTF was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia and significantly changed the structure of the gut microbiota. However, the anti-hyperlipidaemic effect of PTF was not influenced by the co-treatment with antibiotics (ampicillin+norfloxacin). A microbiological analysis of the gut microbiotas revealed that PTF selectively enhanced the relative abundance of Lactobacillus and decreased the relative abundance of Bacteroides and Alistipes. A correlation analysis between biochemical indexes and individual taxon showed that Lactobacillus was negatively associated with serum lipids and glucose while Bacteroides and Alistipes were positively associated with serum lipids and glucose. The modulatory effect of PTF on Lactobacillus, Bacteroides and Alistipes was not disturbed by the administration of antibiotics. Conclusion These results demonstrated that the polyphenol-rich PTF as a unique gut microbiota modulating agent and highlighted the richness of Lactobacillus and the decreased abundance of Bacteroides and Alistipes as an effective indicator of the therapeutic effect of medicinal foods on hyperlipidaemia.

Background & Aims Gut dysbiosis plays a role in hepatic encephalopathy (HE), while its relationship at the acute episode of overt HE (AHE), the disease progression and clinical outcomes remains unclear. We aimed to identify AHE-specific microbiome and its association to patients’ outcomes. Methods We profiled fecal microbiome changes for a cohort of 62 patients with cirrhosis and AHE i) before treatment, ii) 2-3 days after medication and iii) 2-3 months after recovery, and three control cohorts i) healthy individuals, patients with ii) compensated or iii) decompensated cirrhosis. Results Comparison of the microbiome shift from compensated, decompensated cirrhosis, AHE to recovery revealed the AHE-specific gut-dysbiosis. The gut microbiome diversity was decreased during AHE, further reduced after medication, and only partially reversed during the recovery. The relative abundance of Bacteroidetes phylum in the microbiome decreased, whereas that of Firmicute, Proteobacteria and Actinobacteria increased in patients during AHE compared with those with compensated cirrhosis. A total of 70 operational taxonomic units (OTUs) were significantly different between AHE and decompensated cirrhosis abundances. Of them, the abundance of Veillonella parvula increased the most during AHE via a metagenomics recovery of the genomes. Moreover, the relative abundances of three (Alistipes, Bacteroides, Phascolarctobacterium) and five OTUs (Clostridium-XI, Bacteroides, Bacteroides, Lactobacillus, Clostridium-sedis) at AHE were respectively associated with HE recurrence and overall survival during the subsequent one-year follow-up. Conclusions AHE-specific gut OTUs were identified that may be involved in HE development and able to predict clinical outcomes, providing new strategies for the prevention and treatment of HE recurrence in patients with cirrhosis., Graphical abstract

Research on the interaction between dietary vitamins and intestinal bacteria is poorly understood. To investigate the effect of dietary vitamins on the cecal bacterial communities, 2 bacterial 16S rRNA gene clone libraries were constructed from pooled PCR products obtained from the cecal digesta of 28-d broilers fed diets with vitamins (V) at the NRC level or with no vitamins (NV). The results showed that BW gain and average feed intake of V broilers was significantly higher (P < 0.01) than NV broilers, whereas the feed/gain ratio was significantly lower (P < 0.01) in V broilers. A total of 188 and 185 clones were sequenced for the NV and V broilers, respectively. Sequence identity criterion of 98% was used to assign sequences to operational taxonomic units (OTU). Clones from the NV group broilers were assigned to 14 OTU, with 33% clones affiliated with the genus Clostridium, 19% affiliated with the genera Escherichia/Shigella, 14% affiliated with the genus Bacteroides, and the remaining clones (34%) affiliated with 5 other bacterial genera (Faecalibacterium, Parasporobacterium, Ruminococcus, Streptococcus, and Subdoligranulum). Clones from the V group broilers were assigned to 23 OTU, with 46% of the clones affiliated with the genus Clostridium, 11% affiliated with the genus Fecalibacterium, and the remaining clones (43%) affiliated with 8 other genera (Anaerofilum, Lactobacillus, Anaerotruncus, Oscillibacter, Alistipes, Gracilibacter, Acetivibrio, and Haloplasma). Three OTU assigned to Clostridium, Faecalibacterium, and Ruminoccus were shared between the 2 libraries. Shannon diversity index showed the V broilers exhibited significantly higher bacterial diversity (P = 0.05), and Libshuff analysis indicated that the community structure between the 2 groups was significantly different (P < 0.0001). These results suggest that lack of dietary vitamins can increase the ratio of facultative pathogenic bacteria and decrease the diversity of bacteria in the cecum of broilers. Our results provide new leads for further investigations on the interaction between dietary vitamin additives and the gut health of broilers.

Alistipes (previously Bacteroides) are strictly anaerobic gram-negative rods that resemble the Bacteroides fragilis group in that most species are bile-resistant and indole-positive; however, they are only weakly saccharolytic and most species produce light brown pigment only on laked rabbit blood agar. In this retrospective study, we re-identified 18 organisms previously identified phenotypically as "Bacteroides putredinis-like", but that did not produce pigment on routine media. The strains were identified with 16S rDNA sequencing and pigment production was evaluated on several different culture media. Only 12/18 strains had molecular identifications of Alistipes species, while the remaining strains phylogenetically resembled Butyricimonas and Odoribacter spp. Pigment production was not a reliable test for those Alistipes strains that are described as pigment producers.

Lessonia nigrescens inhabits rocky intertidal and shallow subtidal zone, being a crucial brown algae to ecology and economy. L. nigrescens contains a broad range of bioactive compounds, such as fucans and phlorotannins. In this study, the antidiabetic activity of Lessonia nigrescens ethanolic extract was investigated in streptozotocin (SZT)-induced type 2 diabetic mice fed with a high-sucrose/high-fat diet. The components of the intestinal microflora in diabetic mice were analyzed by high-throughput next-generation 16S rRNA gene sequencing. Fasting blood glucose levels in type 2 diabetic mice were significantly decreased after administration of the extract. The histology revealed that the extract could protect the cellular architecture of liver and kidney. The extract significantly increased Bacteroidetes bacteria and decreased Firmicutes populations in intestinal microflora. Specifically, the extract can increase Barnesiella and reduce Clostridium and Alistipes. The increased gene and protein expression levels of PI3K in liver were observed in the extract groups, while the expressions of JNK1 were significantly downregulated by the extract.

Recent treatment guidelines for uncomplicated urinary tract infections (UTIs) discourage fluoroquinolone prescription because of collateral damage to commensal microbiota, but the ecologic impact of alternative agents has not been evaluated by culture-free techniques. We prospectively collected faecal samples at three time points from ambulatory patients with UTIs treated with ciprofloxacin or nitrofurantoin, patients not requiring antibiotics and household contacts of ciprofloxacin-treated patients. We described changes in gut microbiota using a culture-independent approach based on pyrosequencing of the V3-V4 region of the bacterial 16S rRNA gene. All groups were similar at baseline. Ciprofloxacin had a significant global impact on the gut microbiota whereas nitrofurantoin did not. The end of ciprofloxacin treatment correlated with a reduced proportion of Bifidobacterium (Actinobacteria), Alistipes (Bacteroidetes) and four genera from the phylum Firmicutes (Faecalibacterium, Oscillospira, Ruminococcus and Dialister) and an increased relative abundance of Bacteroides (Bacteroidetes) and the Firmicutes genera Blautia, Eubacterium and Roseburia. Substantial recovery had occurred 4 weeks later. Nitrofurantoin treatment correlated with a reduced relative proportion of the genus Clostridium and an increased proportion of the genus Faecalibacterium. This study supports use of nitrofurantoin over fluoroquinolones for treatment of uncomplicated UTIs to minimize perturbation of intestinal microbiota.