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Schistosoma japonicum (S. japonicum) is one of the etiological agents of schistosomiasis, a widespread zoonotic parasitic disease. However, the mechanism of the balanced co-existence between the host immune system and S. japonicum as well as their complex interaction remains unclear. In this study, 16S rRNA gene sequencing, combined with metagenomic sequencing approach as well as ultraperformance liquid chromatography–mass spectrometry metabolic profiling, was applied to demonstrate changes in the gut microbiome community structure during schistosomiasis progression, the functional interactions between the gut bacteria and S. japonicum infection in BALB/c mice, and the dynamic metabolite changes of the host. The results showed that both gut microbiome and the metabolites were significantly altered at different time points after the infection. Decrease in richness and diversity as well as differed composition of the gut microbiota was observed in the infected status when compared with the uninfected status. At the phylum level, the gut microbial communities in all samples were dominated by Firmicutes, Bacteroidetes, Proteobacteria, and Deferribacteres, while at the genus level, Lactobacillus, Lachnospiraceae NK4A136 group, Bacteroides, Staphylococcus, and Alloprevotella were the most abundant. After exposure, Roseburia, and Ruminococcaceae UCG-014 decreased, while Staphylococcus, Alistipes, and Parabacteroides increased, which could raise the risk of infections. Furthermore, LEfSe demonstrated several bacterial taxa that could discriminate between each time point of S. japonicum infection. Besides that, metagenomic analysis illuminated that the AMP-activated protein kinase (AMPK) signaling pathway and the chemokine signaling pathway were significantly perturbed after the infection. Phosphatidylcholine and colfosceril palmitate in serum as well as xanthurenic acid, naphthalenesulfonic acid, and pimelylcarnitine in urine might be metabolic biomarkers due to their promising diagnostic potential at the early stage of the infection. Alterations of glycerophospholipid and purine metabolism were also discovered in the infection. The present study might provide further understanding of the mechanisms during schistosome infection in aspects of gut microbiome and metabolites, and facilitate the discovery of new targets for early diagnosis and prognostic purposes. Further validations of potential biomarkers in human populations are necessary, and the exploration of interactions among S. japonicum, gut microbiome, and metabolites is to be deepened in the future.

Berberine (BBR) has been reported that it has effects on inhibiting colorectal cancer (CRC). However, the mechanism of BBR on CRC also remains largely unknown. Herein, we investigated the therapeutic effects of BBR on CRC from the perspective of gut microbiota and metabolic alterations, which can provide a holistic view to understand the effects of BBR on CRC. First, azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse was used as CRC animal model, then the degree of colorectal carcinogenesis in AOM/DSS mice with or without BBR administration was measured. The composition and abundance of gut microbiota was investigated by using 16S rRNA. Meanwhile, feces samples were analyzed with 1H NMR spectroscopy to investigate the metabolic alterations. As a result, BBR significantly reduced intestinal tumor development with lower macroscopic polyps and ki-67 expression of intestinal tissue, and better colonic morphology in mice. Moreover, BBR altered the composition of gut microbiota in AOM/DSS mice obviously, which were characterized by a decrease of Actinobacteria and Verrucomicrobia significantly at the phylum level. At the genus level, it was able to suppress pathogenic species, such as f_Erysipelotrichaceae, Alistipes, and elevate some short-chain fatty acids (SCFA)-producing bacteria, including Alloprevotella, Flavonifractor, and Oscillibacter. Metabolic data further revealed that BBR induced metabolic changes in feces focus on regulating glycometabolism, SCFA metabolism and amino acid metabolism, which also provides evidence for alteration of the microbiota because these feces metabolites are the products of interactions between the host and the microbial community. This study showed that BBR induced alterations in microbiota and metabolic in AOM/DSS mice, which might providing new insight into the inhibition effects of BBR on CRC.

BackgroundThe factors affecting host-pathogen ecology in terms of the microbiome remain poorly studied. Chickens are a key source of protein with gut health heavily dependent on the complex microbiome which has key roles in nutrient assimilation and vitamin and amino acid biosynthesis. The chicken gut microbiome may be influenced by extrinsic production system parameters such as Placement Birds/m2 (stocking density), feed type and additives. Such parameters, in addition to on-farm biosecurity may influence performance and also pathogenic bacterial numbers such as Campylobacter. In this study, three different production systems ‘Normal’ (N), ‘Higher Welfare’ (HW) and ‘Omega-3 Higher Welfare’ (O) were investigated “in a natural environment” at day 7 and day 30 with a range of extrinsic parameters assessing performance in correlation with microbial dynamics and Campylobacter presence.ResultsOur data identified production system N as significantly dissimilar from production systems HW and O when comparing the prevalence of genera. An increase in Placement Birds/m2 density led to a decrease in environmental pressure influencing the microbial community structure. Prevalence of genera such as Eisenbergiella within HW and O, and likewise Alistipes within N were representative. These genera have roles directly relating to energy metabolism, amino acid, nucleotide and short chain fatty acid (SCFA) utilisation. Thus, an association exists between consistent and differentiating parameters of the production systems, that affect feed utilisation, advance our knowledge of mechanistic underpinnings, leading to competitive exclusion of genera based on competition for nutrients and other factors. Campylobacter was identified within specific production system and presence was linked with the increased diversity and increased environmental pressure on microbial community structure. Addition of Omega-3 though did alter prevalence of specific genera, in our analysis did not differentiate itself from HW production system. However, Omega-3 was linked with a positive impact on weight gain.ConclusionsOverall, our results show that microbial communities in different industrial production systems are deterministic in elucidating the underlying biological confounders, and these recommendations are transferable to farm practices and diet manipulation leading to improved performance and better intervention strategies against Campylobacter within the food chain.Graphical Abstract

The current study employed high-fat diet (HFD) induced murine model to assess the relationship between the lipid-lowering effect of aged citrus peel (chenpi) extract and the alterations of gut microbiota. The results showed that intake of chenpi extract for 12 week dose-dependently suppressed HFD-induced body weight, food intake, Lee's index, together with decreased the level of fasting blood glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol. Moreover, chenpi extract administration up-regulated the abundance and diversity of fecal microbiota and down-regulated the ratio of Firmicutes-to-Bacteroidetes, which was characterized by the lower family of Lachnospiraceae, Helicobacteraceae, and Desulfovibrionaceae, and higher family of Bacteroidales_S24-7, Bacteroidaceae, Rikenellaceae, and Ruminococcaceae. Consistently, at the genus levels, chenpi extract treatment reversed the expansions of Helicobacter, Lachnospiraceae_UCG-006, and Desulfovibrio, while increased the abundance of Bacteroides, Rikenellaceae_RC9_gut_group, and Alistipes (belonging to Rikenellaceae family), Anaerotruncus and Odoribacter (belonging to Ruminococcaceae family), which were significantly negatively correlated with the levels of the serum lipid parameters. In conclusion, our findings indicated that anti-obesity ability of chenpi extract might be related to the improvement of gut microbiota imbalance. PRACTICAL APPLICATIONS: With the improvement of living standards, the incidence of metabolic diseases such as obesity, hypertension, and diabetes has increased significantly, and it has become a public health problem that seriously affects the health of the people. Chenpi contains a large amount of active ingredients, flavonoids, and other compounds, which can promote the absorption of the digestive system and have good effects on diseases such as the cardiovascular system. Our previous study has confirmed that the chenpi extract effectively regulated the glucose and lipid metabolism disorder induced by high-fat diet. However, it is not clear whether the effect is closely related to the improvement of gut microbiota. Accordingly, our result would provide a theoretical basis for future research on the relationship between obesity, chenpi extract, and gut microbiota, and support additional understanding of its potential anti-obesity effects.

Graves’ disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.

The human gut microbiota is involved in host health and disease development. Therefore, lifestyle-related diseases such as hypertension (HT), hyperlipidemia (HL), and type 2 diabetes mellitus (T2D) may alter the composition of gut microbiota. Here, we investigated gut microbiota changes related to these diseases and their coexistence. This study involved 239 Japanese subjects, including healthy controls (HC). The fecal microbiota was analyzed through the isolation of bacterial genomic DNA obtained from fecal samples. Although there were no significant differences in the microbial structure between groups, there was a significant difference in the &alpha, diversity between HC and the patients in whom two diseases coexisted. Moreover, Actinobacteria levels were significantly increased, whereas Bacteroidetes levels were significantly decreased in all disease groups. At the genus level, Bifidobacterium levels were significantly increased in the HL and T2D groups, as were those of Collinsella in all disease groups. In contrast, Alistipes levels were significantly lower in the HL group. Furthermore, metabolic enzyme families were significantly increased in all disease groups. Interestingly, the structure and function of the gut microbiota showed similar profiles in all the studied diseases. In conclusion, several changes in the structure of the gut microbiota are associated with T2D, HT, and HL in Japanese subjects.

Chagas disease is caused by the flagellate protozoan Trypanosoma cruzi. Cardiomyopathy and damage to gastrointestinal tissue are the main disease manifestations. There are data suggesting that the immune response to T. cruzi depends on the intestinal microbiota. We hypothesized that Chagas disease is associated with an altered gut microbiome and that these changes are related to the disease phenotype. The stool microbiome from 104 individuals, 73 with Chagas disease (30 with the cardiac, 11 with the digestive, and 32 with the indeterminate form), and 31 healthy controls was characterized using 16S rRNA amplification and sequencing. The QIIME (Quantitative Insights Into Microbial Ecology) platform was used to analyze the data. Alpha and beta diversity indexes did not indicate differences between the groups. However, the relative abundance of Verrucomicrobia, represented primarily by the genus Akkermansia, was significantly lower in the Chagas disease groups, especially the cardiac group, compared to the controls. Furthermore, differences in the relative abundances of Alistipes, Bilophila, and Dialister were observed between the groups. We conclude that T. cruzi infection results in changes in the gut microbiome that may play a role in the myocardial and intestinal inflammation seen in Chagas disease.

Ziziphus Jujuba cv. Pozao has been consumed as a traditional fruit with regional characteristics in China for a long time; however, fewer studies on polysaccharides from Ziziphus Jujuba cv. Pozao (JP) have been documented. This study aimed to evaluate the effect of oral administration of JP on cyclophosphamide-induced ICR mice for 28 days. The results showed that oral administration of JP could significantly improve the lymphocyte proliferation in the spleen and decrease the proportion of CD3+ and CD4+ and the ratio of CD4+/CD8+ in cyclophosphamide-induced mice in a dose-dependent manner. JP treatment also increased the levels of IL-2, IL-4, IL-10, IFN-γ, and TNF-α in serum and the intestine, and the improvement effects were proportional to the dose of JP. Similarly, JP significantly increased the levels of IgA and SIgA, as well as the expressions of Claudin-1 and Occludin in the intestine. Particularly, the expressions of Claudin-1 and Occludin were the best in the M-JP group. Furthermore, JP positively regulated the gut microbiota as indicated by the enriched microbiota diversity. At the phylum level, the relative abundance of Firmicutes was significantly decreased by JP, while that of Bacteroidetes was increased by JP treatment. More importantly, the ratio of Firmicutes/Bacteroidetes was significantly increased. And a high dose of JP is the most effective. At the genus level, the abundances of the Bacteroidales-S24-7-group, Lachnospiraceae, Alloprevotella, Alistipes and Bacteroides were increased by JP treatment. These results provided evidence for the regulating effect of JP on the peripheral immunity and intestinal barrier function in cyclophosphamide-induced hypoimmune mice.

Gut microbiota has been shown to play critical roles in host health. The present study was to determine the toxicological effects of microcystin-LR (MCLR) on gut microbial community and metabolites using 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS). MCLR was administered to BALB/c mice by gavage for eight weeks. Results of the microbial alpha-diversity (Sobs, Chao1, ACE and Shannon indexes) decreased in MCLR-treated group versus controls. Phylum Candidatus Saccharibacteria decreased significantly in MCLR-treated group versus controls. Correspondingly, more than thirties genera in relative abundance decreased, especially short chain fatty acid (SCFA)-producing bacteria (e.g., Alistipes and Ruminococcus). These results indicated that the gut microbial community structure was remarkably changed by MCLR. Furthermore, concentrations of SCFAs were significantly decreased after MCLR exposure (P

The gut microbiome has been implicated in a variety of physiological states. Controversy over causality, however, has always haunted microbiome studies. Here, we utilized the bidirectional Mendelian randomization (MR) approach to address questions that are not yet mature for more costly randomized interventions. From a total of 3,432 Chinese individuals with shotgun sequencing data for whole genome and whole metagenome, as well as anthropometric and blood metabolic traits, we identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 out of the 58. Gut microbiome could determine features in the blood. For example, increased fecal relative abundances of Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration, and fecal microbial module pectin degradation might increase serum uric acid. On the other hand, blood features may determine gut microbial features, e.g. glutamic acid appeared to decrease Oxalobacter, and a few members of Proteobacteria were unidirectionally influenced by cardiometabolically important metabolites such as 5-methyltetrahydrofolic acid, alanine, as well as selenium. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies. The results are consistent with whole-body cross-talks of the microbiome and the circulating molecules.

Simple Summary Bone health is an important factor in broiler production. Among the key nutrients affecting bone health, phosphorus (P) plays a great role. Enterococcus faecium has been widely used as feed additive to promote growth performance of broilers. There were reports suggesting that E. faecium improved skeletal health of rats. However, the effect of E. faecium on the bones of broilers remains unclear. The present study is to investigate the effect of E. faecium on P absorption and utilization in broilers and the associated changes in the gut microbiota. Dietary inclusion with E. faecium did not improve broiler performance in this study but improved P absorption and bone mineralization. In E. faecium-treated broilers, the expression of intestinal type IIb sodium-dependent phosphate cotransporter (NaP-IIb) mRNA was upregulated and the concentration of serum alkaline phosphatase was increased. Dietary supplementation with E. faecium changed the gut microbiota populations of broilers and increased the relative abundance of SCFA (short-chain fatty acid)-producing bacteria. The changed populations of microbiota improved intestinal P absorption and bone forming metabolic activities. In conclusion, dietary inclusion with E. faecium facilitates increased utilisation of P in broilers. Abstract Modern broiler chickens have ongoing bone health problems. Phosphorus (P) plays an important role in bone development and increased understanding of P metabolism should improve the skeletal health of broilers. Enterococcus faecium has been widely used as a probiotic in broiler production and is shown to improve skeletal health of rats, but its effect on the bones of broilers remains unclear. This study investigated the effect of E. faecium on P absorption and utilization in broilers and the associated changes in the gut microbiota using 16S rDNA sequencing. Dietary supplementation with E. faecium improved P absorption through upregulation of the expression of intestinal NaP-IIb mRNA and increased the concentration of serum alkaline phosphatase. These actions increased P retention and bone mineralization in E. faecium-treated broilers. The positive effects of E. faecium on P metabolism were associated with changes in the populations of the intestinal microbiota. There was increased relative abundance of the following genera, Alistipes, Eubacterium, Rikenella and Ruminococcaceae and a decrease in the relative abundance of Faecalibacterium and Escherichia-Shigella. Dietary supplementation with E. faecium changed gut microbiota populations of broilers, increased the relative abundance of SCFA (short-chain fatty acid)-producing bacteria, improved intestinal P absorption and bone forming metabolic activities, and decreased P excretion. E. faecium facilitates increased utilisation of P in broilers.

Gut microbiota plays a fundamental role in the pathogenesis of metabolic disorders, including obesity. Gut microbial dysbiosis induces immune and metabolic disturbances. We wanted to find out a gut microbiota composition at adolescents with obesity and normal weight. The examined group included 40 adolescents. There were 18 obese adolescents with SDS BMI=2.77±0.55 (OB), and 22 adolescents with SDS BMI=0.01±0.50 (CO). The metagenome sequencing of V3-V4 variable regions of 16S rDNA was done by Novogene Company (China). Data were analyzed using the StatSoft STATISTICA 6.0 software package. Statistical significance was accepted at the p

Growing literature details the critical importance of the microbiome in the modulation of human health and disease including both the gastrointestinal and genitourinary systems. Rectovaginal fistulae (RVF) are notoriously difficult to manage, many requiring multiple attempts at repair before correction is achieved. RVF involves two distinct microbiome communities whose characteristics and potential interplay have not been previously characterized and may influence surgical success. In this pilot study, rectal and vaginal samples were collected from 14 patients with RVF. Samples were collected preoperatively, immediately following surgery, 6–8 weeks postoperatively and at the time of any fistula recurrence. Amplification of the 16S rDNA V3-V5 gene region was done to identify microbiota. Data were summarized using both α-diversity to describe species richness and evenness and β-diversity to characterize the shared variation between communities. Differential abundance analysis was performed to identify microbial taxa associated with recurrence. The rectal and vaginal microbiome in patients undergoing successful fistula repair was different than in those with recurrence (β-diversity, p = 0.005 and 0.018, respectively) and was characterized by higher species diversity (α-diversity, p = 0.07 and p = 0.006, respectively). Thirty-one taxa were enriched in patients undergoing successful repair to include Bacteroidetes, Alistipes and Rikenellaceae as well as Firmicutes, Subdoligranulum, Ruminococcaceae UCG-010 and NK4A214 group. Microbiome characteristics associated with fistula recurrence have been identified. The association of higher vaginal diversity with a favorable outcome has not been previously described. Expansion of this pilot project is needed to confirm findings. Taxa associated with successful repair could be targeted for subsequent therapeutic intervention.

Background In animals, many factors affect the small intestinal function and cecal microorganisms, including body weight and genetic background. However, whether paternal weight impacts the small intestinal function and cecal microorganisms remains unknown to date. The current study used Nonghua sheldrake to estimate the effect of paternal weight on the intestine of the offspring by evaluating differences in small intestinal morphology, digestive enzyme activity, and cecal microorganisms between the offspring of male parents with high body weight (group H) and that of male parents with low body weight (group L). Results The results of the analysis of small intestinal morphology showed that the villus height of the jejunum of group H ducks was higher than that of group L ducks, and the difference was significant for ducks at 10 weeks of age. Moreover, the villus height/crypt depth of the duodenum in group H significantly exceeded that of group L at a duck age of 2 weeks. The amylase activity in the jejunum content of group H exceeded that of group L at 5 and 10 weeks of age. Furthermore, the proportion of the Firmicutes to Bacteroidetes was significantly higher in group H (duck age of 2 weeks). Among the genera with a relative abundance exceeding 1%, the relative abundances of genera Desulfovibrio, Megamonas, Alistipes, Faecalibacterium, and Streptococcus observed in group H were significantly different between group H and group L. Conclusions For the first time, this study identifies the effect of paternal weight on offspring small intestinal function and cecal microorganisms. Consequently, this lays a foundation for further research on the relationship between male parents and offspring intestinal function.

Recent studies have highlighted the role of gut microbiota in the pathogenesis of cardiometabolic diseases. In particular, microbially produced metabolites have been shown to affect the host metabolism, however, their impacts on metabolic diseases have not been fully elucidated. For instance, the findings from an obese mouse model have suggested that polysaccharide fermentation could serve as the additional energy sources, yet the effects on human pathology has not been reported. To address this question, we applied a multi-omics strategy, which integrated gut microbiome analyses with multi-platform metabolomic techniques. We sampled from 306 Japanese males and females with obesity (49.7%) and prediabetes (32.7%). Fecal microbiome was analyzed by 16S rRNA amplicon and metagenomic shot-gun sequencings, while fecal hydrophilic and lipid metabolites were measured using GC-MS and LC-MS-based platforms respectively, and were clustered by their co-expression profiles. We found that three out of 19 fecal hydrophilic clusters and three out of 86 lipid clusters were significantly associated with insulin resistance (IR) defined by HOMA-IR. Notably, the identified fecal hydrophilic clusters were classified as sugar derivatives such as monosaccharides and disaccharides. These metabolites were indeed increased in not only the fecal contents but also the plasma samples of IR group. In addition, microbes belonging to genera Dorea and Coprococcus, which are known to degrade polysaccharides, were abundant in the IR group, and were highly correlated with fecal sugar derivatives, while other microbes such as Alistipes showed negative correlation. Finally, we confirmed that the oral administration of a Dorea strain to HFD-fed mice exacerbated obesity and IR compared with Alistipes administration. Collectively, we report a novel mechanistic insight into the effects of gut microbes on metabolic diseases, where microbial fermentation of polysaccharides and its derivatives impact the host metabolism. Disclosure T. Takeuchi: None. Y. Nakanishi: None. K. Ikeda: None. H. Tsugawa: None. W. Suda: None. Y. Mizuno: None. N. Yamamichi: None. M. Arita: None. M. Hattori: None. N. Kubota: None. T. Kubota: None. T. Kadowaki: Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Cosmic Corporation, Daiichi Sankyo, Eli Lilly Japan K.K., FUJIFILM, Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Medscape Education, Medtronic, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, NIPRO Medical Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Asahi Mutual Life Insurance. S. Koyasu: None. H. Ohno: None.

BACKGROUND Gastrointestinal (GI) difficulties are very common among children with cerebral palsy (CP) and comorbid epilepsy. GI function is influenced by dietary structure on gut microbiota. The aim of this study was to compare gut microbiota differences in two dietary groups of this population and examine whether such differences are related to GI dysfunction. METHODS Forty children with CP and epilepsy were recruited from a social welfare center, including 23 consuming a fluid diet (liquid diet group) and 17 consuming a normal diet (general diet group). Bacterial DNA was extracted from feces, the V3-V4 region of the 16S rRNA gene was amplified from the DNA, and high-throughput sequencing of the amplified sequences was performed. Microbe prevalence levels were compared on multiple phylogenic levels. RESULTS Gut microbial populations differed substantially between the liquid diet group and general diet group. The only two phyla that differed significantly between the two groups were Bacteroidetes (p = 0.034) and Actinobacteria (p = 0.013). Regarding representation of genera, Prevotella species were selectively predominant in the general diet group (25.849% vs. 3.612% in the liquid diet group, p

The gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of LPS, with day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, we observed significant alterations. Neonatal mice had high relative abundances ofStreptococcus,EscherichiaandEnterococcusand increased primary bile acids. In contrast, older mice were dominated byCandidatusArthromitus,AlistipesandLachnoclostridium, and had increased concentrations of SCFAs and methyamines. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.

Background Graves’ disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive. Objective To investigate the association and mechanism between intestinal flora and GD. Methods We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation. Results The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy. Conclusions Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.

To study the intestinal microbiota changes in patients with bronchial asthma (BA).40 patients and 15 healthy individuals were included for the study. The microbiota study in feces samples was performed by sequencing the 16SpRNA gene.It was noted an increasing of theProteobacteriaproportion in the patients with BA. The fractions ofBetaproteobacteriaиGammaproteobacteriawere increased in the patients with allergic BA and at the same time, only theGammaproteobacteriapart was increased in patients with non-allergic form of BA. It was found an increase inBacilliand a decrease in the proportion bacteria forming butyrate (Anaerostipes, Faecalibacterium) and acetate (Alistipes), which was corresponded to a decrease in the proportion of strict anaerobic symbionts and an increase in the proportion of opportunistic facultative anaerobes. The relative bacteria amount was reduced for theNegativicutes Erysipelotrichia, Bacteroidia classes, theErysipelotrichaceae,Pseudomonadaceae, Rhodospirillaceae, Bacillaceae familiesand for the kinds ofBarnesiella, Paraprevotella, Pyrolobus, Bifidobacterium, Pseudomonas, Coprobacter, Bacillusin the allergic asthma patients with syndrome of intensive bacterial overgrowth (SIBO) cases. In the non-allergic asthma case, the presence of SIBO was accompanied by the relative bacteria amount increasing of theBacteroidaceaeand theParaprevotellafamilies and theOdoribacter,Bacteroides, Butyricicoccus, Parasutterellagenera. The bacterial spectrum changes correlated with the main clinical and laboratory manifestations of BA in the patients.The results have indicated the differences in the intestinal microflora composition of healthy volunteers and patients with bronchial asthma in including the SIBO presence. It is necessary more detail study of the bacterial composition changes in the intestine for the bronchopulmonary pathology case.Цель. Изучить изменения кишечной микробиоты у пациентов с бронхиальной астмой (БА). Материалы и методы. В исследование включены 40 больных БА и 15 клинически здоровых лиц. Исследование микробиоты в образцах кала выполнено с помощью секвенирования гена 16SрPНК. Результаты. У пациентов с БА отмечены увеличение доли Proteobacteria (Betaproteobacteria и Gammaproteobacteria при аллергической и только Gammaproteobacteria при неаллергической астме), увеличение Bacilli и снижение доли бактерий, образующих бутират (Anaerostipes, Faecalibacterium) и ацетат (Alistipes), что соответствует уменьшению доли строгих анаэробов-симбионтов и увеличению доли условно-патогенных факультативных анаэробов. В случае наличия синдрома избыточного бактериального роста (СИБР) при аллергической астме снижено относительное количество бактерий классов Negativicutes, Erysipelotrichia, Bacteroidia, семейств Erysipelotrichaceae, Pseudomonadaceae, Rhodospirillaceae, Bacillaceae, родов Barnesiella, Paraprevotella, Pyrolobus, Bifidobacterium, Pseudomonas, Coprobacter, Bacillus. При неаллергической астме наличие СИБР сопровождалось повышением относительного количества бактерий семейства Bacteroidaceae, родов Paraprevotella, Odoribacter, Bacteroides, Butyricicoccus, Parasutterella. Изменения бактериального спектра коррелировали с основными клинико-лабораторными проявлениями БА. Заключение. Полученные результаты свидетельствуют о различиях состава микрофлоры кишечника здоровых добровольцев и больных БА, в том числе при наличии СИБР. Необходимо дальнейшее изучение изменений бактериального состава кишечника при бронхолегочной патологии.

A water-soluble polysaccharide named CYP-1 was isolated from Chinese yam. CYP-1 was characterized as a mannoglucan having a backbone consisting predominately of 1,4-α-linked Glcp branched at O-2, O-3, and O-6 position by t-α-linked Manp with a molecular weight of 2.86 kDa. CYP-1 could inhibit the overproduction of pro-inflammatory cytokines (such as TNF-α and IL-1β) in LPS-induced RAW 264.7 cells and DSS-induced colitis mice. Oral administration of CYP-1 dramatically alleviated colonic pathological damage, suppressed the activation of colonic inflammatory signaling pathways (such as NF-κB and NLRP3 inflammasome), recovered the mRNA expression of junctional proteins (such as ZO-1, claudin-1, occludin, and connexin-43), and modulated the gut microbiota by decreasing the abundances of Alistipes, Helicobacter, and an unidentified Enterobacteriaceae, in DSS-induced colitis mice. Overall, the present study elucidated that a new polysaccharide structure CYP-1 from Chinese yam and its therapeutic potential as a prebiotic for the prevention of inflammatory bowel disease.

Prader&ndash, Willi syndrome is a rare genetic disorder associated with impaired body composition, hyperphagia, and excessive weight gain. Strict dietary restrictions from an early age is crucial to prevent or delay the early onset of obesity, which is the main driver of comorbidities in these patients. The aim of this study was to identify dietary and gut microbiota components closely linked to weight status of these patients. We studied a cohort of children and adolescents with genetic diagnosis of Prader&ndash, Willi syndrome (N = 31), in which we determined adiposity by Dual-energy X-ray absorptiometry (DXA) and dietary composition with 4-day food records. Furthermore, we obtained fecal samples to assess microbiota composition by 16S sequencing. Multivariate regression models showed that body mass index standard deviation score (BMI-SDS) and body fat mass were directly associated with saturated fat intake and meat consumption, and inversely associated with fruit consumption. Furthermore, the gut microbiome from normal weight patients was characterized by higher phylogenetic diversity compared to those overweight or obese, with differential abundance of several genera, including Alistipes, Klebsiella, and Murimonas. Notably, Alistipes abundance was inversely correlated to adiposity, lipid and glucose homeostasis parameters, and meat intake. Our results suggest that limiting meat and increasing fruit intake might be beneficial for body weight management in children and adolescents with Prader&ndash, Willi syndrome.

Dysbiosis of gut microbiota during the progression of HBV-related liver disease is not well understood, as there are very few reports that discuss the featured bacterial taxa in different stages. The aim of this study was to reveal the featured bacterial species whose abundances are directly associated with HBV disease progression, that is, progression from healthy subjects to, chronic HBV infection, chronic hepatitis B to liver cirrhosis. Approximately 400 fecal samples were collected, and 97 samples were subjected to 16S rRNA gene sequencing after age and BMI matching. Compared with the healthy individuals, significant gut microbiota alterations were associated with the progression of liver disease. LEfSe results showed that the HBV infected patients had higher Fusobacteria, Veillonella, and Haemophilus abundance while the healthy individuals had higher levels of Prevotella and Phascolarctobacterium. Indicator analysis revealed that 57 OTUs changed as the disease progressed, and their combination produced an AUC value of 90% (95% CI: 86–94%) between the LC and non-LC groups. In addition, the abundances of OTU51 (Dialister succinatiphilus) and OTU50 (Alistipes onderdonkii) decreased as the disease progressed, and these results were further verified by qPCR. The LC patients had the higher bacterial network complexity, which was accompanied with a lower abundance of potential beneficial bacterial taxa, such as Dialister and Alistipes, while they had a higher abundance of pathogenic species within Actinobacteria. The compositional and network changes in the gut microbiota in varied CHB stages, suggest the potential contributions of gut microbiota in CHB disease progression.

Purpose To investigate the effect of total glucoside of paeony (TGP) on gut microbiota in NOD mice with Sjögren’s syndrome (SS), using high-throughput sequencing of 16SrRNA gene. Methods Twenty-four NOD mice were randomly assigned to 4 groups (n = 6 per group): sham group receiving deionized water (0.4 ml), hydroxychloroquin group receiving hydroxychloroquin (0.4 ml), TGP group receiving TGP (0.4 ml), and TGP + hydroxychloroquin group receiving 0.4 ml TGP and 0.4 ml hydroxychloroquin. Balb/c mice (n = 6) receiving 0.4 ml deionized water were used as a control group. After intragastric injection of drugs for 8 weeks, feces were collected for high-throughput sequencing of 16SrRNA gene. Results The sequencing of 16SrRNA gene resulted in 3686 OTUs, and 10 phyla and 69 genera were identified. Compared with the control group, the indices of Chao, Ace and Shannon in the other 4 groups were significantly lower (P Conclusions TGP increases the growth of many key beneficial bacteria, inhibits the growth of dominant pathogenic bacteria, and increases the diversity and abundance of gut microorganisms, especially when combined with hydroxychloroquine. Our findings suggest that TGP may be effective to treat SS by improving the microecological structure of the gut.

Microplastics (MPs) have become a severe concern in marine environment worldwide. Micro-polystyrene particles have been proved to accumulate in vivo and caused disorders of digestion, antioxidant system, immunity and intestinal microflora, but little is known about the effects of nano-polystyrene (nano-PS). In order to understand response mechanism of marine fish to nano-PS, the effects of nanoplastics on the intestinal health and growth performance of the juvenile Larimichthys crocea were investigated. After 14-d exposure, the reduced digestive enzyme activities indicated that nano-PS had a negative impact on the digestion and absorption of juvenile fish. Moreover, analysis of the intestinal microbiota showed that the proportion of the three-dominant bacterial phyla (Bacteroidetes, Proteobacteria and Firmicutes) in the gut changed significantly, accompanied by a significant increase of potentially pathogenic bacteria (Parabacteroides and Alistipes). In addition, lysozyme activity and specific growth rate (SGR) were significantly reduced, and total mortality of juvenile fish was significantly increased. Overall, nano-PS exposure was harmful for the health of juvenile fish, which might threaten their population in the long term.

OBJECTIVE: HIV-1-associated dysbiosis is most commonly characterized by overall decreased diversity, with abundance of the genus Prevotella, recently related to inflammatory responses. DESIGN: A pilot study including 10 antiretroviral therapy-treated HIV-1-infected men and 50 uninfected controls was performed to identify the main gut dysbiosis determinants (e.g. Prevotella enrichment), that may affect mucosal antiviral defenses and T cell immunity in HIV-1-infected individuals. METHODS: 16rRNA gene sequencing was applied to the HIV-1-infected individuals' fecal microbiota and compared with controls. Measurements of CD4 and CD8 T cell activation [CD38, human leukocyte antigen (HLA)-DR, CD38 HLA-DR] and frequencies of Th17, obtained from lamina propria lymphocytes isolated from five different intestinal sites, were performed by flow cytometry. IFNβ, IFNAR1 and MxA gene expression level was evaluated by real-time PCR in lamina propria lymphocytes. Nonparametric t tests were used for statistical analysis. RESULTS: HIV-1-infected men had a significant fecal microbial communities' imbalance, including different levels of genera Faecalibacterium, Prevotella, Alistipes and Bacteroides, compared with controls. Notably, Prevotella abundance positively correlated with frequencies of CD4 T cells expressing CD38 or HLA-DR and coexpressing CD38 and HLA-DR (P

Aims. Hashimoto’s thyroiditis (HT), a type of autoimmune disease, occurs due to genetic predisposition and environmental factors. It is well known that thyroid function may affect the gut microbiota. However, the composition of gut microbiota in HT patients with different thyroid function status has been less highlighted. Therefore, we focused on the alterations in the composition of gut microbiota in HT patients with euthyroidism and hypothyroidism. Methods. We performed a cross-sectional study, including 45 HT patients with euthyroidism, 18 HT patients with hypothyroidism, and 34 healthy controls. Fecal samples were collected, and microbiota was examined by using 16S RNA ribosomal RNA gene sequencing. Then, we analyzed the possible pathways in relation to the enriched bacteria by linear discriminant analysis (LDA) effect size (LEfSe). Results. Compared with the controls, bacterial richness and diversity were significantly lower in patients with HT, especially in hypothyroidism. Moreover, Lachnospiraceae_incertae_sedis, Lactonifactor, Alistipes, and Subdoligranulum were more enriched in HT patients with euthyroidism, while Phascolarctobacterium was more abundant in those with hypothyroidism. Further analysis suggested that Phascolarctobacterium was negatively related to several pathways, including environmental information processing and metabolism. Conclusion. In summary, our study demonstrated the altered composition of gut microbiota in HT patients with different thyroid function status. Moreover, Phascolarctobacterium may be involved in the development of HT.

Although it is generally accepted that dietary fiber is health promoting, the underlying immunological and molecular mechanisms are not well defined, especially with respect to cellulose, the most ubiquitous dietary fiber. Here, the impact of dietary cellulose on intestinal microbiota, immune responses and gene expression in health and disease was examined. Lack of dietary cellulose disrupted the age-related diversification of the intestinal microbiota, which subsequently remained in an immature state. Interestingly, one of the most affected microbial genera was Alistipes which is equipped with enzymes to degrade cellulose. Absence of cellulose changed the microbial metabolome, skewed intestinal immune responses toward inflammation, altered the gene expression of intestinal epithelial cells and mice showed increased sensitivity to colitis induction. In contrast, mice with a defined microbiota including A. finegoldii showed enhanced colonic expression of intestinal IL-22 and Reg3γ restoring intestinal barrier function. This study supports the epidemiological observations and adds a causal explanation for the health promoting effects of the most common biopolymer on earth.

Changes in the intestinal flora composition is referred to as dysbiosis, which is related to obesity development, thus supporting the potential roles of nutrients acting on intestinal flora to exert salutary effects on energetic metabolism of host. Dietary fiber has been known to affect the composition of intestinal flora. The aim of the present study was to investigate the functional effects of konjac flour (KF) on obesity control in respect to improving inflammation, metabolism, and intestinal barrier function, and the possible association of the effects with intestinal flora composition changes. Mice (n = 30) were randomly divided into control group (n = 10), high-fat-diet (HFD) group (n = 10), and KF intervention group (n = 10), followed by feeding for 12 weeks and with adding a KF daily supplementation for the treatment group. Body weight, fat accumulation, inflammation, and energetic metabolism markers in multiple tissues and the gut microbiota of the mice were examined at the end of the experiment. The KF supplementation significantly reduced the gains in weight, fat mass, as well as adipocyte size of HFD mice and lowered the serum TC, leptin (LEP), thiobarbituric acid-reacting substance (TBARS), IL-6, and lipopolysaccharide (LPS) levels in HFD mice. KF also upregulated the expression of intestinal mucosa protein gene Intection and tight junction ZO-1 in HFD mice, as well as upregulate the expression of energy metabolism genes PPARα and CPT-1 as well as the fat metabolism gene HLS in livers and fat tissues, and downregulate that of fat synthesis gene PPARγ (p

International audience; The objectives of this work are to address the prebiotic effects of chicory (Cichorium intybus) together with its possible role in appetite control. We compared nine chicory genotypes in order to determine if variations in the content of metabolites in the roasted roots would lead to modifications in release of satiety hormones and in composition of gut microbiota. To this aim, a 5-week dietary-intervention study was achieved using mice fed with distinct chicory-based preparations. A 16S rRNA gene-based metagenetic analysis of fecal microbiota was performed. In vitro gastrointestinal digestions were performed in order to study the effect of chicory intestinal digests on gut hormone regulation in enteroendocrine cells. Firmicutes/ Bacteroidetes ratio and gut bacterial groups, such as Alloprevotella, Blautia, Alistipes, and Oscillibacter, were found to be modulated by chicory. On the other hand, CCK and GLP-1 satiety hormones were demonstrated to be significantly increased by chicory in vitro.

Background The gut microbiota is closely associated with gastrointestinal (GI) motility disorder, but the mechanism(s) by which bacteria interact with and affect host GI motility remains unclear. In this study, through using metabolomic and metagenomic analyses, an animal model of neonatal maternal separation (NMS) characterized by accelerated colonic motility and gut dysbiosis was used to investigate the mechanism underlying microbiota-driven motility dysfunction. Results An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency. Increase of SLCFAs was positively correlated with elevated abundances of Prevotella, Lactobacillus, and Alistipes. Functional annotation found that the level of bacterial LCFA biosynthesis was highly enriched in NMS group. Essential synthetic genes Fabs were largely identified from the genera Prevotella, Lactobacillus, and Alistipes. Pseudo germ-free (GF) rats receiving fecal microbiota from NMS donors exhibited increased defecation frequency and upregulated bacterial production of intracolonic SLCFAs. Modulation of gut dysbiosis by neomycin effectively attenuated GI motility and reduced bacterial SLCFA generation in the colon lumen of NMS rats. Conclusions These findings reveal a previously unknown relationship between gut bacteria, intracolonic SLCFAs, and host GI motility, suggesting the importance of SLCFA-producing bacteria in GI motility disorders. Further exploration of this relationship could lead to a precise medication targeting the gut microbiota for treating GI motility disorders. Electronic supplementary material The online version of this article (10.1186/s40168-018-0492-6) contains supplementary material, which is available to authorized users.

Background Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics. Results We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival. Conclusions These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT. Electronic supplementary material The online version of this article (10.1186/s40168-018-0474-8) contains supplementary material, which is available to authorized users.

The research included the study of influence of ultrafine particle preparations (nanoparticles of copper, zinc, iron, CuZn alloy) and metal salts (iron pyrophosphate, copper asparginate, zinc asparginate) on the composition of cecal microbiota of broiler chickens. Before adding the studied nanoparticles and metal salts to the diet, cecal microbiota of broiler chickens was represented by 76% Firmicutes taxon and 16% Bacteroidetes. Numerous among them were the bacteria of the taxa Anaerotruncus spp., Lactobacillus spp., Blautia spp., Alistipes spp., and Bacteroides spp.; they constituted 18, 17, 11, and 6%, respectively. A peculiarity of action of the most analyzed metals in nanoform and in the form of salts was a decrease in the number of phylum Firmicutes bacteria and an increase in the number of microorganisms of the phylum Bacteroidetes. The number of bacteria belonging to the families Ruminococcaceae (III, IV, V, VII, and VIII groups), Bacteroidaceae (in all experimental groups), and Lachnospiraceae (I, IV, V, and VII groups) was registered within the taxa of Firmicutes and Bacteroidetes. At the same time, in some experimental groups, the number of bacteria of the family Lachnospiraceae (II, III, and VIII) decreased in the intestine. The data obtained can be used to assess the possibility of using metal nanoparticles in the poultry diet, as a micronutrient preparation, to correct dysbiosis and to improve the utilization of fodder energy.

Objective Dysbiosis is a common feature in the pathogenesis of inflammatory bowel diseases (IBD). Environmental factors, such as vitamin D deficiency, seem to play a role in the intestinal inflammation of IBD. The aim of this study was to investigate whether vitamin D administration has an impact on the bacterial composition in Crohn's disease (CD) compared to healthy controls (HC). Methods A prospective, longitudinal, controlled interventional analysis was conducted in seven patients with CD in clinical remission and 10 HC to investigate the effect of orally administrated vitamin D on the intestinal bacterial composition using 16S ribosomal RNA gene amplicon sequencing. Clinical parameters were assessed. Results In contrast to HC, microbial communities of CD patients changed significantly during early vitamin D administration. However, a further increase in vitamin D level was associated with a reversal of this effect and additionally with a decrease in the bacterial richness in the CD microbiome. Specific species with a high abundancy were found during vitamin D administration in CD, but not in HC; the abundancy of Alistipes, Barnesiella, unclassified Porphyromonadaceae (both Actinobacteria), Roseburia, Anaerotruncus, Subdoligranulum and an unclassified Ruminococaceae (all Firmicutes) increased significantly after 1-week vitamin D administration in CD. Conclusions Vitamin D has a specific influence on the bacterial communities in CD, but not in HC. Administration of vitamin D may have a positive effect in CD by modulating the intestinal bacterial composition and also by increasing the abundance of potential beneficial bacterial strains.

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.

Maternal immune activation (MIA) increases the risk of autism spectrum disorder (ASD) in offspring. Microbial dysbiosis is associated with ASD symptoms. However, the alterations in the brain–gut–microbiota axis in lipopolysaccharide (LPS)-induced MIA offspring remain unclear. Here, we examined the social behavior, anxiety-like and repetitive behavior, microbiota profile, and myelination levels in LPS-induced MIA rat offspring. Compared with control offspring, MIA male rat offspring spent less time in an active social interaction with stranger rats, displayed more anxiety-like and repetitive behavior, and had more hypomyelination in the prefrontal cortex and thalamic nucleus. A fecal microbiota analysis revealed that MIA offspring had a higher abundance of Alistipes, Fusobacterium, and Ruminococcus and a lower abundance of Coprococcus, Erysipelotrichaies, and Actinobacteria than control offspring, which is consistent with that of humans with ASD. The least absolute shrinkage and selection operator (LASSO) method was applied to determine the relative importance of the microbiota, which indicated that the abundance of Alistipes and Actinobacteria was the most relevant for the profile of defective social behavior, whereas Fusobacterium and Coprococcus was associated with anxiety-like and repetitive behavior. In summary, LPS-induced MIA offspring showed an abnormal brain–gut–microbiota axis with social behavior deficits, anxiety-like and repetitive behavior, hypomyelination, and an ASD-like microbiota profile.

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.

Scope Epidemiological studies show a consistent and compelling association between the risk of colorectal cancer development and obesity, but its mechanisms remain poorly understood. Evidence is mounting that colorectal cancer could be prevented by nutritional supplements, such as phytochemicals. Garcinol, a polyisoprenylated benzophenone derivative, is widely present in Garcinia plants. We investigated the potential role of garcinol supplementation in ameliorating obesity-induced colon cancer development. Methods and results An animal model to investigate the effect of high-fat-diet (HFD)-induced obesity on promoting colitis-associated colon cancer (AOM (azoxymethane)/DSS (dextran sodium sulfate)-induced) was designed. The results showed that HFD could promote colitis-associated colon cancer as compared to an AOM/DSS group without the intervention of obesity, and supplementing with 0.05% garcinol in the diet could significantly ameliorate obesity-promoted colon carcinogenesis. The results also revealed that the microbiota composition of each group was significantly different and clustered. The most representative genera were Alistipes, Romboutsia, and Ruminococcus. The RNA-sequencing results showed that the administration of garcinol could regulate genes and improve obesity-promoting colitis-associated colon carcinogenesis. Conclusion Our results suggest that garcinol can prevent obesity-promoted colorectal cancer, and these findings provide important niches for the future development of garcinol as functional foods or adjuvant therapeutic agents. This article is protected by copyright. All rights reserved.

The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21–29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM.

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.

Background Salmonella is one of the most significant food-borne pathogens to affect humans and agriculture. While it is well documented that Salmonella infection triggers host inflammation, the impacts on the gut environment are largely unknown. A CBA/J mouse model was used to evaluate intestinal responses to Salmonella-induced inflammation. In parallel, we evaluated chemically induced inflammation by dextran sodium sulfate (DSS) and a non-inflammation control. We profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from fecal and cecal samples. These data were correlated to the inflammation marker lipocalin-2 and short-chain fatty acid concentrations. Results We demonstrated that inflammation, chemically or biologically induced, restructures the chemical and microbial environment of the gut over a 16-day period. We observed that the ten mice within the Salmonella treatment group had a variable Salmonella relative abundance, with three high responding mice dominated by >46% Salmonella at later time points and the remaining seven mice denoted as low responders. These low- and high-responding Salmonella groups, along with the chemical DSS treatment, established an inflammation gradient with chemical and low levels of Salmonella having at least 3 log-fold lower lipocalin-2 concentration than the high-responding Salmonella mice. Total short-chain fatty acid and individual butyrate concentrations each negatively correlated with inflammation levels. Microbial communities were also structured along this inflammation gradient. Low levels of inflammation, regardless of chemical or biological induction, enriched for Akkermansia spp. in the Verrucomicrobiaceae and members of the Bacteroidetes family S24-7. Relative to the control or low inflammation groups, high levels of Salmonella drastically decreased the overall microbial diversity, specifically driven by the reduction of Alistipes and Lachnospiraceae in the Bacteroidetes and Firmicutes phyla, respectively. Conversely, members of the Enterobacteriaceae and Lactobacillus were positively correlated to high levels of Salmonella-induced inflammation. Conclusions Our results show that enteropathogenic infection and intestinal inflammation are interrelated factors modulating gut homeostasis. These findings may prove informative with regard to prophylactic or therapeutic strategies to prevent disruption of microbial communities, or promote their restoration. Electronic supplementary material The online version of this article (doi:10.1186/s40168-017-0264-8) contains supplementary material, which is available to authorized users.

Mannose-binding lectin (MBL) deficiency is a common innate immune system deficiency, and is associated with exacerbations and increased colonization of some pathogens. However, the response of the gut microbiota, a pivotal factor in host health, to MBL deficiency is not clear. In this study, MBL-/- and wild-type (WT) mice were generated by backcrossing from MBL-A and MBL-C knockout (KO) mice, and fecal samples were collected at different ages (4th, 8th, 12th, 19th and 27th weeks). The gut microbiota was analyzed by high-throughput sequencing with universal 16S rDNA primers (V3-V5 region). The results showed that structural segregation of the gut microbiota occurred at the 8th, 12th, 19th and 27th weeks of age, although there were no significant differences in alpha diversities between MBL-/- and WT mice at different ages. Impressively, in MBL-/- mice, Akkermansia (from the family Verrucomicrobiaceae) were decreased significantly, Lactobacillus (from the family Lactobacillaceae) abundances, Alistipes and Rikenella (both from the family of Rikenellaceae) were always enriched. Network analysis showed that more interactions existed in the gut microbiota from WT mice (33 nodes and 70 edges) than in the gut microbiota from MBL-/- mice (23 nodes and 40 edges). The 16S rDNA function prediction results indicated that the abundances of predicted genes in the "immune system disease", "metabolic disease" and "nucleotide metabolism" pathways were significantly increased in the MBL-/- mice. In conclusion, this study revealed that the gut microbiota changed in MBL deficient mice, especially at ages older than 4 weeks.

We investigated the effect of a combination treatment with dapagliflozin (Dapa), a sodium-glucose cotransporter-2 inhibitor and butyrate on weight change in db/db mice. Six-week-old male db/db mice were assigned to four groups: vehicle with normal chow diet (NCD), Dapa with NCD, vehicle with 5% sodium butyrate-supplemented NCD (NaB), or Dapa with 5% NaB. After six weeks of treatment, faecal microbiota composition was analysed by sequencing 16S ribosomal RNA genes. In the vehicle with NaB and Dapa + NaB groups, body weight increase was attenuated, and amount of food intake decreased compared with the vehicle with the NCD group. The Dapa + NaB group gained the least total and abdominal fat from baseline. Intestinal microbiota of this group was characterized by a decrease of the Firmicutes to Bacteroidetes ratio, a decrease of Adlercreutzia and Alistipes, as well as an increase of Streptococcus. In addition, the proportion of Adlercreutzia and Alistipes showed a positive correlation with total fat gain, whereas Streptococcus showed a negative correlation. Inferred metagenome function revealed that tryptophan metabolism was upregulated by NaB treatment. We demonstrated a synergistic effect of Dapa and NaB treatment on adiposity reduction, and this phenomenon might be related to intestinal microbiota alteration.

Previous studies showed that probiotics supplementation contributed to alleviate obesity. This work was to assess the efficacy of Lactobacillus plantarum FRT10 from sour dough in alleviating obesity in mice fed with a high-fat diet (HFD), and the underlying mechanisms focusing on modulation of the gut microbiota profile. Kunming mice were fed with a regular diet (CT), a high-fat diet (HFD), and two HFDs containing low and high doses of L. plantarum FRT10 for 8 weeks. The physiological and biochemical modulations in liver were analyzed. Cecal contents were analyzed by high-throughput 16S ribosomal RNA sequencing. FRT10 supplementation significantly reduced body weight gain, fat weight, and liver triacylglycerols (TGs) and alanine aminotransferase (ALT) concentrations (P

The gut microbiota, including pathogenic microorganisms and probiotics, has been involved in tumor initiation and progression by regulating the components of intestinal flora. Canmei formula (CMF), a traditional Chinese medicine, chronicled in the Chuang Yang Jing Yan Quan Shu, has been clinically used as an adjuvant therapy to treat patients with colorectal carcinoma (CRC) in China. In this study, we investigate the treatment effect of CMF in the azoxymethane (AOM) and dextran sodium sulfate (DSS) induced and high-fat diet augmented colitis-associated colorectal cancer in vivo, and explore its mechanism of action. We found that CMF treatment relieved the inflammation and alteration of the gut microbiota and significantly inhibited the development of intestinal adenoma. Linear discriminant analysis showed that the flora diversity in the normal mice, model mice and CMF treatment mice was different. At the family level, the relative abundance of Desulfovibrionaceae decreased in CMF groups. The relative abundance of Desulfovibrionaceae were lower in the CMF groups than in model group, whereas Rikenellaceae and Alistipes were increased. Altogether our results indicate that CMF treatment ameliorate colitis-associated colorectal carcinogenesis by modulating the composition of the gut microbiota in vivo.

Background Flavonoids are reported to modulate the composition of gut microbiota, which play an important role in preventing obesity and associated metabolic diseases. In this study, we investigated the effect of Total Flavonoids of Quzhou Fructus Aurantii Extract (TFQ) on gut microbial community in mice fed with a high-fat diet (HFD). Methods C57BL/6J mice were fed with either a chow diet or HFD with or without oral gavage of TFQ (300 mg/kg/day) for 12 weeks. Results Our data indicate TFQ significantly reduced obesity, inflammatio,n and liver steatosis. TFQ elevates the expression of tight junction proteins and reduces metabolic endotoxemia. In addition, TFQ treatment reverses HFD-induced gut dysbiosis, as indicated by the reduction of Firmicutes to Bacteroidetes ratio, the increase of genera Akkermansia and Alistipes, and the decrease of genera Dubosiella, Faecalibaculum, and Lactobacillus. Conclusion These findings support a prebiotic role of TFQ as a dietary supplement for the intervention of gut dysbiosis and obesity-related metabolic disorders.

Evidence has proven that the gut microbiota is an important environmental factor contributing to obesity by altering host energy harvest and storage. We performed a high-throughput 16S rDNA sequencing association study and serum metabolomics profiling in rats with a high-sugar diet. Our studies revealed that the high sugar diet reduced the diversity of cecal microorganisms, while the combination of theabrownin and the high sugar diet increased the diversity of cecal microorganisms and promoted reproduction of Alloprevotella, Coprostanoligenes_group, Bacteroides, Prevotellaceae_NK3B31_group, Desulfovibrio, Intestinimonas, Alistipes, Bifidobacterium, Phascolarctobacterium, Ruminococcaceae_UCG-010 and Staphylococcus. The combination also inhibited the growth of Lactobacillus, Prevotellaceae_Ga6A1_group and Tyzzerella. The Firmicutes/Bacteroidetes (F/B) ratio can be significantly reduced after the intervention of theabrownin in high sugar diet rats, and the reproduction of Bacteroides acidifaciens (BA) and Staphylococcus saprophyticus subsp. saprophyticus can be promoted. We found that the obesity-associated gut microbial species were linked to the changes in circulating metabolites. Serum levels of deoxycholic acid, cholic acid, 1H-indole-3-acetic acid, 3-indole acrylic acid and melatonin were negatively correlated with BA and Staphylococcus saprophyticus subsp. saprophyticus, but positively correlated with Lactobacillus murinus, Leptum and Gut_metagenome. 2-Hydroxy-6-methylpyridin-3-carboxylic acid, l-homoserine, and 1,7-dimethylxanthine were positively correlated with BA and Staphylococcus saprophyticus subsp. saprophyticus, but negatively correlated with Lactobacillus murinus, Leptum, and Gut_metagenome. In a high sugar diet mode, theabrownin reduced the body weight and triglycerides and improved insulin resistance mainly by targeting the reproduction of intestinal microorganisms such as BA, Staphylococcus saprophyticus subsp. saprophyticus, Lactobacillus murinus, Leptum, Gut_metagenome and so on. A strong correlation between cecal microorganisms and serum metabolites, obesity and insulin resistance was observed. Theabrownin has high potential in reducing the risk of cardiovascular diseases such as diabetes and obesity.