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It was our hypothesis that foods high in polyphenols and fiber have prebiotic activity. This human intervention study aimed to determine if daily consumption of freeze-dried California strawberry powder (SBP) leads to changes in the intestinal microbiota, fecal cholesterol and bile acid (BA) microbial metabolites. Fifteen healthy adults consumed a beige diet+26 g of SBP for 4 weeks, followed by 2 weeks of beige diet only. Stool samples were collected at 0, 4, and 6 weeks. Fecal microbiota was analyzed by 16S rRNA sequencing; fecal cholesterol, BA, and microbial metabolites by gas chromatography. Confirming compliance, urine concentration of pelargonidin, urolithin A glucuronide and dimethylellagic acid glucuronide were present after 4 weeks of SBP consumption. Daily SBP altered the abundance of 24 operational taxonomic units (OTUs). Comparing week 4 to baseline the most significant increases were observed for one OTU from Firmicutes\Clostridia\ Christensenellaceae\NA, one OTU from Firmicutes\ Clostridia\Mogibacteriacea\NA, one OTU from Verrucomicrobia\ Verrucomicrobiaceae\Akkermansia\Muciniphila, one OTU from Actinobacteria\ Bifidobacteriaceae\Bifidobacterium\NA, and one OTU from Bacteroidetes\Bacteroidia\ Bacteroidaceae\Bacteroides and decrease of one OTU from Proteobacteria\ Betaproteobacteria\Alcaligenaceae\Sutterella. Comparing week 4 to 6, we observed a reversal of the same OTUs from C Christensenellaceae, V muciniphilia and C Mogibacteriaceae. Fecal short chain fatty acids and most of the fecal markers including cholesterol, coprostanol, primary and secondary BAs were not changed significantly except for lithocholic acid, which was increased significantly at week 6 compared to baseline. In summary, SBP consumption increased the abundance of gut microorganisms related to lean body weight, health and longevity, and increased fecal lithocholic acid at week 6 in healthy study participants.

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.

Ethnopharmacological relevance Sijunzi decoction (SJZD) is a classic recipe in traditional Chinese medicine (TCM) to strengthen the spleen and replenish Qi. It is well known for treating disorders of gastrointestinal function manifested in poor appetite, reduced food intake and loose stools. Polysaccharide is the most abundant constituent and the major effective component in SJZD. Aim of the study The present study aimed to understand the immunomodulatory mechanism of S-3–1, a homogeneous polysaccharide purified from SJZD with immune-enhancement activity, by investigating its effects on human intestinal microbes and short chain fatty acids. Materials and methods S-3–1 was incubated with simulated gastric juice, intestinal juice, and human fecal microflora independently and sequentially. The concentrations of total polysaccharide and reducing sugar were measured to identify the stability of independently and sequentially incubated S-3–1 in three in vitro fermentation models. Gas chromatograph (GC) analysis was used to measure the short chain fatty acid (SCFA) contents in human fecal samples. The human gut microbiota composition was measured by 16S rRNA gene Illumina MiSeq sequencing (V3-V4 region). Results S-3–1 was degraded in three in vitro fermentation models separately and sequentially. Both S-3–1 and incubated S-3–1 could regulate the abundances of Lactobacillus, Pediococcus, Streptococcus, Bacteroides, Enterococcus, Clostridium and Dorea in human intestinal microflora samples. Specifically, S-3–1 could only regulate the abundances of Paraprevotella and Oscillospira, while the influenced flora changed to Butyricimonas, Coprococcus, Dialister, Sutterella, Ruminococcus and Parabacteroides after sequential incubation of S-3–1. In contrast to S-3–1 showing no influence on the content of SCFA, incubated S-3–1 showed increased contents of acetic acid and total acid that were associated with its effects on the abundances of Enterococcus, Sutterella, Butyricimonas and Streptococcus. Conclusion S-3–1 plays an immunomodulatory role by regulating the abundances of 9 intestinal bacteria genera. Incubated S-3–1 can regulate more bacteria genera, a total of 13 kinds, and can adjust the SCFA content to affect immunomodulation. Incubation with gastric and intestinal juices enhanced S-3–1′s capability of modulating the intestinal flora composition and decreased the bacteria’s need for a carbon source. This study could provide new insights for studies on the pharmacological mechanisms of polysaccharides in vitro.

Several studies have demonstrated the effect of probiotics on prevention of diseases in infants. However, the mechanisms remain not fully addressed. In the present study a modified standard ileal efflux medium (SIEM) was exploited in an in vitro analysis and the effect of Lactobacillus plantarum ST-III on the composition of infant gut microbiota was examined in I-chip analysis followed by qPCR confirmation. Also, the effect of ST-III, when administered in combination with breast milk and infant formula, was investigated. The results showed that ST-III could reduce the overall amount of Enterobacteria and Bacteroidetes bacteria, yet increase the abundance of Lactobacillus and certain Bifidobacterium species. Notably, some species/genus of bacteria of medical significance, e.g., Alcaligenaceae sutterella and Desulfovibrio bacteria were inhibited by ST-III. Moreover, co-administration of breast milk or infant formula could increase the abundance of ST-III, suggesting a synergistic effect between ST-III and infant formula and breast milk.

Pumpkin polysaccharide is able to alleviate diabetes, but understanding of the underlining mechanism is still limited. In this study, we hypothesized that the alleviating effects of pumpkin polysaccharide is modulated via changes in the gut microbiota and short-chain fatty acid (SCFA) production in type 2 diabetic rats. After the type 2 diabetic model successfully was established, three groups of high-fat diet induced diabetic rats were intragastrically administered pumpkin polysaccharide, metformin, or saline solution respectively. We utilized 16S rRNA gene sequencing and multivariate statistics to analyze the structural and key species of gut microbiota in the type 2 diabetic rats. The results revealed that pumpkin polysaccharide alleviated the type 2 diabetes by improving the insulin tolerance and decreasing the levels of serum glucose (GLU), total cholesterol (TC), and low-density lipoprotein (LDL-C), while increasing the levels of high-density lipoprotein (HDL-C). Simultaneously, pumpkin polysaccharide changed the structure of gut microbiota and had selective enrichment in key species of Bacteroidetes, Prevotella, Deltaproteobacteria, Oscillospira, Veillonellaceae, Phascolarctobacterium, Sutterella, and Bilophila. The correlations between the key species and SCFA production indicated the underlining mechanisms of pumpkin polysaccharide on type 2 diabetes.

The consumption of a high-fat diet can cause metabolic syndrome and induces host gut microbial dysbiosis and non-alcoholic fatty liver disease (NAFLD). We evaluated the effect of polyphenol-rich jaboticaba peel and seed powder (JPSP) on the gut microbial community composition and liver health in a mouse model of NAFLD. Three-month-old C57BL/6 J male mice, received either a control (C, 10% of lipids as energy, n = 16) or high-fat (HF, 50% of lipids as energy, n = 64) diet for nine weeks. The HF mice were randomly subdivided into four groups (n = 16 in each group), three of which (HF-J5, HF-J10, and HF-J15) were supplemented with dietary JPSP for four weeks (5%, 10%, and 15%, respectively). In addition to attenuating weight gain, JPSP consumption improved dyslipidemia and insulin resistance. In a dose-dependent manner, JPSP consumption ameliorated the expression of hepatic lipogenesis genes (AMPK, SREBP-1, HGMCoA, and ABCG8). The effects on the microbial community structure were determined in all JPSP-supplemented groups; however, the HF-J10 and HF-J15 diets led to a drastic depletion in the species of numerous bacterial families (Bifidobacteriaceae, Mogibacteriaceae, Christensenellaceae, Clostridiaceae, Dehalobacteriaceae, Peptococcaceae, Peptostreptococcaceae, and Ruminococcaceae) compared to the HF diet, some of which represented a reversal of increases associated with HF. The Lachnospiraceae and Enterobacteriaceae families and the Parabacteroides, Sutterella, Allobaculum, and Akkermansia genera were enriched more in the HF-J10 and HF-J15 groups than in the HF group. In conclusion, JPSP consumption improved obesity-related metabolic profiles and had a strong impact on the microbial community structure, thereby reversing NAFLD and decreasing its severity., This work was financially supported by Brazilian funding: FAPERJ – Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ: E-26/202.677/2018, E-26/010.002203/2019) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES) – Finance code 001. Benjamin Willing was supported by the Canada Research Chair Program and his laboratory received funding from the Canadian Natural Science and Engineering Research Council (NSERC)

Gut-Brain Axis provides a bidirectional communicational route, an imbalance of which can have pathophysiological consequences. Differential gut microbiome studies have become a frontier in autism research, affecting 85% of autistic children. The present study aims to understand how gut microbiota of autism subjects differ from their neurotypical counterparts. This study would help to identify the abundance of bacterial signature species in autism and their associated metabolites. 16S rRNA metagenomic sequence datasets of 30 out of 206 autism subjects were selected from the American Gut Project Archive. First, the taxonomic assignment was inferred by similarity-based methods using the Quantitative Insights into Microbial Ecology (QIIME) toolkit. Next, species abundance was characterized, and a co-occurrence network was built to infer species interaction using measures of diversity. Thirdly, statistical parameters were incorporated to validate the findings. Finally, the identification of metabolites associated with these bacterial signature species connects with biological processes in the host through pathway analysis. Gut microbiome data revealed Akkermansia sp. and Faecalibacterium prausnitzii to be statistically lower in abundance in autistic children than their neurotypical peers with a five and two-fold decrease, respectively. While Prevotella sp. and Sutterella sp. showed a five and a two-fold increase in cases, respectively. The constructed pathway revealed succinate and butyrate as the significant metabolites for the bacterial signature species identified. The present study throws light on the role of mucosa-associated bacterial species: Veillonella sp., Prevotella sp., Akkermansia sp., Sutterella sp., Faecalibacterium prausnitzii, Lactobacillus sp., which can act as diagnostic criteria for detection of gut dysbiosis in autism., Highlights • Bacteroidetes/Firmicutes ratio is significantly higher in autistic children due to differential lifestyle habits in the present study. • Mucosal associated bacteria, namely Prevotella, Akkermansia, Veillonella, Sutterella, and Faecalibacterium are indicated as potential diagnostic criteria for gut dysbiosis in autism. • Elevated Proteobacteria levels is contrasting with reported inclinations towards gut related functionality in mouse models. • The authors report unique link for autism and Prevotella sp. phylotype with higher relative abundance in autism cases. • Pathway revealed succinate and butyrate as the significant metabolites for the identified bacterial signatures.

Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4 weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27 days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes / Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila , both Proteobacteria , abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα, was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation.

The prevalence of atopic dermatitis (AD) has increased and a therapeutic strategy using probiotic intervention has been reported. The effects of different Bifidobacterium (B. breve, B. bifidum, B. animalis, B. infants, and B. adolescentis) on gut microbial changes were explored in 2,4-dinitrofluorobenzene (DNFB)-induced AD, a T helper type 2-dominant allergic disease. Oral administration of Bifidobacterium suppressed skin thickening and mast cell infiltration, blocked pro-inflammatory cytokines (IL-4, CCL11, IL-13, and CCL22), increased IL-10 and IFN-γ, and modulated the microbiome and ecology in the gut. Based on 16S rRNA results, DNFB treatment resulted in gut microbial dysbiosis, characterized by a decrease in the proportion of Firmicutes and an increase in Bacteroidetes. The core microbiome related to AD were also observed (Dorea, Prevotella, Sutterella, Odoribacter, and Pseudomonas). B. breve and B. bifidum treatments increased the relative abundance of Adlercreutzia, Streptococcus, Lactobacillus, Anaerostipes, and Anaerotruncus. The functional modules involved in fructose and mannose metabolism, propanoate metabolism, and fatty acid biosynthesis were upregulated, and these might be related to immune regulation and short-chain fatty acids (SCFA) production. Taken together, these results suggested that Bifidobacterium treatments affected gut microbial composition and structure, altered gut microbial ecosystem, and these alterations were closely associated with inflammation and SCFA production.

As many inflammatory and metabolic disorders have been associated with structural deficits of the human gut microbiota, the principles and mechanisms that govern its initialization and development are of considerable scientific interest and clinical relevance. However, our current understanding of the developing gut microbiota dynamics remains incomplete. We carried out a large-scale, comprehensive meta-analysis of over 1900 available metagenomic shotgun samples from neonates, infants, adolescents, and their families, using our recently introduced SameStr program for strain-level microbiota profiling and the detection of microbial strain transfer and persistence. We found robust associations between gut microbiota composition and age, as well as delivery mode which was measurable for up to two years of life. C-section was associated with increased relative abundances of non-gut species and delayed transition from a predominantly oxygen-tolerant to intolerant microbial community. Unsupervised networks based on shared strain profiles generated family-specific clusters connecting infants, their siblings, parents and grandparents and, in one case, suggested strain transfer between neonates from the same hospital ward, but could also be used to identify potentially mislabeled metagenome samples. Following birth, larger quantities of strains were shared between vaginally born infants and their mothers compared to C-section infants, which further persisted throughout the first year of life and belonged to the same bacterial species as strains that were shared between adults and their parents. Irrespective of delivery type, older children shared strains with their mothers and fathers and, into adulthood, could be accurately distinguished from unrelated sample pairs. Prominent gut commensal bacteria were both among frequently transferred (e.g. Bacteroides and Sutterella) and newly acquired taxa (e.g. Blautia, Faecalibacterium, and Ruminococcus). Our meta-analysis presents a more detailed and comprehensive picture of the highly dynamic neonatal and infant gut microbiota development than previous studies and presents evidence for taxonomic and functional compositional differences early in life between infants born naturally or by C-section, which persist well into adolescence.

A number of studies have identified that gut microbiota influences the development of cancer. However, there is little known about gut microbiota and esophageal cancer (EC). The aim of this study was to investigate the gut microbiota profile associated with EC. In this study, 23 patients with EC and 23 sex- and age-matched healthy controls (NC) were recruited between July 2019 and August 2019 at Huai'an First People's Hospital (Huai'an, China) and the gut microbiota was analyzed by 16S rRNA gene sequencing of fresh stool samples. We found that the microbial richness of intestinal flora in patients with EC were higher than NC, whereas evenness did not change obviously. Principal coordinate analysis (PCoA) and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) analysis both revealed that a distinct separation in bacterial community composition between the EC and NC. At the phylum level, the EC group showed significantly higher abundances of Firmicutes and Actinobacteria, but a lower Bacteroidetes than NC. At the genus level, a significantly increased abundance of Streptococcus, Bifidobacterium, Subdoligranulum, Blautia, Romboutsia, Collinsella, Paeniclostridium, Dorea, and Atopobium were observed in EC patients, while Lachnospira, Bacteroides, Agathobacter, Lachnoclostridium, Parabacteroides, Paraprevotella, Butyricicoccus, Tyzzerella, Fusicatenibacter, and Sutterella were reduced. Receiver operating characteristic (ROC) analysis revealed that Lachnospira, Bacteroides, Streptococcus, and Bifidobacterium both achieved a high accuracy in EC diagnosis (area under the curve was more than 0.85), and the Lachnospira was found to be the best classifier. This study firstly characterized the gut microbiota composition of EC patients and screened out the optimal potential microbiota biomarkers for EC diagnosis. It may provide a fundamental reference for further studies on the gut microbiome for the diagnosis and treatment of EC.

Objective The use of probiotics to reduce mortality of sepsis was supported by a series of clinical research subjects. However, the exact mechanisms underlying protective effects of probiotic in sepsis has not been elucidated clearly. The aim of this study was to explore the therapeutic effects of Lactobacillus rhamnosus GG (LGG) prophylaxis on the host co-microbiota and metabolism in mice with sepsis-induced colon microbiota dysbiosis. Methods Mice were fed either probiotic LGG or saline 4 wk before cecum ligation and puncture (CLP) operation. Fecal samples were collected and analyzed by 16S rDNA sequencing and ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS)–based metabolomics. Results LGG treatment could noticeably reduce the mortality of sepsis and reverse gut microbiota dysbiosis caused by sepsis. Specifically, LGG reduced conditional pathogenic bacteria, such as Proteobactria and Deferribacteres; lipopolysaccharide producers like Enterobacteriaceae, facultative anaerobes, including Bacteroidaceae and Erysipelotrichaceae, and increased the abundance of bacteria related to energy harvest, such as Firmicutes; colon barrier restorers like Akkermansia; and liver function regulators like Coprococcus and Sutterella. Furthermore, the changes in fecal metabolites were prevented by LGG. These changes were found mainly to be correlated with the bile acid and metabolism pathways, lysophosphatidylcholines metabolism, and eicosatetraenoic acid metabolism. Finally, correlation analysis shown that microbiota dysbiosis was closely related to metabolic imbalance. Conclusions Probiotic LGG may has a positive effect on reducing mortality of sepsis through rebalancing the metabolic profiles and gut microbiota.

Purpose To investigate whether there are differences in diversity, taxonomic composition, and predicted functional pathways of the gut microbiome between Island Hispanic Puerto Ricans (HPR) and mainland non-Hispanic whites (NHW) measured before and at the end of chemo-radiation (CRT) for Rectal Cancer. Methods Fifty-six stool samples of newly diagnosed rectal cancer patients (25 HPR and 31 NHW) were amplicon-sequenced during chemo-radiotherapy. 16S rRNA gene data was analyzed using QIIME2, phyloseq, and LEfSe. Results We observed similar within-sample alpha diversity for HPR and NHW participants during CRT. However, at the end of CRT, several taxa were present at significantly different abundances across both groups. Taxa enriched in the gut of HPR compared to NHW included Muribaculaceae, Prevotella 2 and 7, Gemella, Bacillales Family XI, Catenibacterium, Sutterella, Pasteurellales, and Pasteurellaceae genera, whereas over-represented taxa in NHW participants were Turicibacter and Eubacteriaceae. Significant differences in predicted HPR microbiota functions included pathways for synthesis of L-methionine and degradation of phenylethylamine and phenylacetate. Conclusion In this pilot study, taxonomic analyses and functional predictions of the gut microbiomes suggest greater inflammatory potential in gut microbial functions among HPR rectal cancer patients undergoing CRT compared to that of NHW participants.

Background & Aims Depression and anxiety are frequent comorbidities with inflammatory bowel diseases (IBD). Alterations to the intestinal microbiome promote not only intestinal inflammation but also psychologic function. We studied the interactions between the composition of the intestinal microbiota and psychological outcomes in patients with IBD in Switzerland. Methods We performed a prospective study of psychological comorbidities and quality of life (QoL) in 171 participants in the Swiss IBD Cohort Study with IBD in remission. Participants complete the Hospital Anxiety and Depression Scale, Perceived Stress Questionnaire, the 36-Item Short Form Survey, and the IBD QoL Questionnaire. Microbes were collected from intestinal biopsies and analyzed by 16S rRNA high-throughput sequencing. Results Microbiomes of patients with higher perceived stress had significantly lower alpha diversity. Anxiety and depressive symptoms were significantly associated with beta diversity. We found a negative correlation between psychological distress and abundance of Clostridia, Bacilli, Bacteroidia, and Beta- and Gamma-proteobacteria. Psychological distress was also associated with decreases in operational taxonomic units from the lineages of Lachnospiraceae, Fusobacteriaceae, Ruminococcaceae, Veillonellaceae, Alcaligenaceae, Desulfovibrionaceae, and Bacteroidaceae families. The relative abundance of Bifidobacterium in patients with Crohn's disease and Desulfovibrio in patients with ulcerative colitis correlated with depression, whereas abundance of Sutterella, RF 32, and Lactococcus correlated with quality of life in patients with Crohn's disease. Conclusions We identified correlations between the composition of the intestinal microbiota in patients with IBD and remission, psychological well-being, and QoL. Further studies should investigate how intestinal inflammation, the microbiome, and microbial metabolites affect psychological well-being and whether these components are mono- or bi-directionally linked.

Background: The gut microbiome is known to change following HIV infection. However, previous studies have generated inconsistent results regarding the differences in the gut microbiome between HIV positive and negative individuals. Methods: A bioinformatics analysis was performed on nine 16S rRNA gene sequencing data generated from 1082 stool samples (646 from HIV positive individuals and 436 from HIV negative individuals). We compared the differences in the gut microbiome between HIV positive and negative individuals across various factors. Results: The diversity of the gut microbiome differed between HIV positive and negative individuals with respect to age, gender, and whether or not antiretroviral therapy (ART) was initiated. Our analysis showed that ART did not restore the diversity of the gut microbiome. HIV infection changed the dominant genera of the intestine such that the prevalence of Prevotella increased and that of Bacteroides decreased in HIV positive individuals, especially in men who have sex with men (MSMs). Sutterella, Butyricimonas, Lachnospira etc. had significant correlations with the number of CD4+T cells and HIV viral load. In addition, the differentially enriched genera were found to be associated with functional pathways that correlated with ART. Conclusions: This study explored the changes in the gut microbiome in HIV positive individuals and revealed the association between differentially enriched genera and functional pathways involved in ART, which might help to elucidate the effects of HIV infection on the human gut microbiome. Funding Statement: This study was supported by the National Natural Science Foundation of China (NSFC, 81660334), Guangxi Natural Science Foundation (2017GXNSFAA198190, 2018GXNSFAA050099), National Key Science and Technology Project of China (2018ZX10101002-001-006). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors stated: "Reusable data for our analysis complied with all relevant ethical regulations."

Cancer represents a major disease burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent important causes of therapeutic failure. There is growing evidence that the gut microbiota can affect the response to chemo- and immunotherapeutic drugs by modulating efficacy and/or toxicity, and diet is the most important factor affecting the gut microbiota. In this study, we assessed the auxiliary antitumor effects of immunomodulatory fungal proteins from Hericium erinaceus (HEP) administered with the chemotherapy drug 5-fluoro-2,4(1H,3H)-pyrimidinedione (5-Fu), and we attempted to identify new potential prebiotic bacteria for auxiliary antitumor treatment. There were 1455 proteins identified from Hericium erinaceus. In a xenografted mouse model of cancer, HEP with 5-Fu significantly suppressed tumor growth, inhibited inflammatory factors such as interferon (IFN)-γ, interleukin (IL)-1Β, IL-2, IL-6, tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS), and regulated the expression of Akt, CCDN1, CKD4, FOXM1, MMP7, MYC, PPAR-α and PPAR-γ. 16S rRNA sequencing showed that HEP ameliorated the dysbacteriosis induced by 5-Fu, as it inhibited certain aerobic and microaerobic bacteria including Parabacteroides, Flavobacteriaceae, Christensenellaceae, Anoxybacillus, Aggregatibacter, Comamonadaceae, Planococcaceae, Desulfovibrionaceae, Sporosarcina, Staphylococcus, Aerococcaceae and Bilophila in the xenografted mice, and increase some probiotic bacteria such as Bifidobacterium, Gemellales, Blautia, Sutterella, Anaerostipes, Roseburia, Lachnobacterium, Lactobacillus and Desulfovibrio. This demonstrates that HEP can significantly promote the antitumor efficacy of 5-Fu by improving the microbiota composition, immune inflammatory response and homeostasis and by activating the PPAR signaling pathway. Funding: This work was supported by funding from the National Natural Science Foundation of China (81701086), the Guangzhou Science and Technology Plan Projects (201504281708257; 201604020009; 201707020022), and the High-level Leading Talent Introduction Program of GDAS (2016GDASRC-0102; 2017GDASCX-0102). Declaration of Interest: All the authors declare that no competing interests exist. Ethical Approval: The experimental protocols were approved by the Guangdong Laboratory Animals Monitoring Institute, and all experimental procedures conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

OBJECTIVES: Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in human infants and young farm animals. Osteopontin (OPN), a glycoprotein present in high concentration in human milk, has immunomodulatory functions, which could indirectly impact the microbiota. Furthermore, a previous study has shown fecal microbiota composition differs between wild-type and OPN knockout mice. Herein, the effects of OPN-enriched algae on the gut microbiota composition and volatile fatty acid (VFA) concentrations of ETEC-infected piglets were assessed. METHODS: Naturally-farrowed piglets were sow-reared for 21 days and then randomized to two weaning diets: WT (formula + 1% wild-type algae) or OPN (formula + 1% OPN-enriched algae). On postnatal day (PND) 31, all piglets were infected orally with a live culture of ETEC (10(10) colony-forming unit/3 mL dose) daily for three consecutive days. On PND 41, ascending colon (AC) contents were collected. Gut microbiota was assessed by sequencing V3-V4 regions of 16S rRNA gene and VFAs were determined by gas chromatography. Alpha-diversity and VFAs were analyzed using PROC MIXED procedure of SAS. Beta-diversity was evaluated by permutational multivariate analysis of variance (PERMANOVA) and differential abundance analysis on the bacterial genera was performed using DESeq2 package of R. RESULTS: Shannon indices were lower in the AC contents of OPN piglets compared to WT piglets. The overall colonic microbiota of OPN piglets differed from that of WT piglets (PERMANOVA P = 0.015). At genus level, OPN-enriched algae increased the abundance of Streptococcus, decreased the abundances of Sutterella, Candidatus Soleaferrea, dga-11 gut group, Rikenellaceae RC9 gut group, Ruminococcaceae UCG-010, unculturedRuminococcaceae, Prevotella 2 and 7 compared to piglets consuming wild-type algae (P

independent techniques to evaluate the microbial composition of pouch and afferent limb tissue biopsies from patients with variable pouch outcomes. Methods: Patients with confirmed UC or familial adenomatous polyposis(FAP) who had a colectomy and IPAA, with ileostomy closure ≥1 year prior to study enrollment were recruited from Mount Sinai Hospital at the time of follow-up endoscopy. Retrospective and cross-sectional clinical/endoscopic information was collected at the time of enrollment and patients were classified into 4 groups: FAP/ no pouchitis(FAP), UC/no pouchitis(NP), UC/pouchitis(P) andUC/CD-like phenotype(CDL). P was defined based on the mPDAI. CDL diagnosis was based on presence of afferent limb inflammation or fistula. 2 biopsies were collected and snap-frozen in liquid nitrogen (1 afferent limb and 1 pouch). Microbial DNA was extracted and sequenced using the 454 GS FLX Titanium Sequencing system using primers specific for the V1-V3 and V2-V3 hypervariable regions of 16S rRNA genes in 2 batches. Sequences were quality trimmed and aligned to a SILVA reference database using mothur, with a minimum bootstrap cutoff of 80%. A threshold level of 0.05 was used to assign sequence clusters to a specific genus and patients were considered positive for genera with counts >0. Dichotomized results were analyzed using Fisher's exact test and Bonferroni correction for multiple testing. Results: 245 patients were recruited to the study of whom 79 were selected for analysis with complete data available (18 FAP, 21 NP, 20 P, 20 CDL). Analysis at the genus level showed that Blautia was detected significantly less often in the P group in both afferent limb (p=0.002) and pouch samples (p=0.008) compared to the other groups. Bacteroides and Sutterella were significantly less frequent among P and CDL groups in the pouch samples only (p=0.001 and 0.01 respectively). There was no significant difference in the proportions of these genera between outcome groups in the different batches. Conclusion: Differences in microbial composition are associated with outcomes following IPAA. Specifically, the genera Blautia, Bacteroides and Sutterella were found less frequently in patients with P and CDL compared to those without pouchitis. Further study may allow us to identify the role these organisms play in pouch pathogenesis, and to identify interactions occurring between microorganisms and host endogenous elements such as genotype and development of anti-microbial antibodies.

independent techniques to evaluate the microbial composition of pouch and afferent limb tissue biopsies from patients with variable pouch outcomes. Methods: Patients with confirmed UC or familial adenomatous polyposis(FAP) who had a colectomy and IPAA, with ileostomy closure ≥1 year prior to study enrollment were recruited from Mount Sinai Hospital at the time of follow-up endoscopy. Retrospective and cross-sectional clinical/endoscopic information was collected at the time of enrollment and patients were classified into 4 groups: FAP/ no pouchitis(FAP), UC/no pouchitis(NP), UC/pouchitis(P) andUC/CD-like phenotype(CDL). P was defined based on the mPDAI. CDL diagnosis was based on presence of afferent limb inflammation or fistula. 2 biopsies were collected and snap-frozen in liquid nitrogen (1 afferent limb and 1 pouch). Microbial DNA was extracted and sequenced using the 454 GS FLX Titanium Sequencing system using primers specific for the V1-V3 and V2-V3 hypervariable regions of 16S rRNA genes in 2 batches. Sequences were quality trimmed and aligned to a SILVA reference database using mothur, with a minimum bootstrap cutoff of 80%. A threshold level of 0.05 was used to assign sequence clusters to a specific genus and patients were considered positive for genera with counts >0. Dichotomized results were analyzed using Fisher's exact test and Bonferroni correction for multiple testing. Results: 245 patients were recruited to the study of whom 79 were selected for analysis with complete data available (18 FAP, 21 NP, 20 P, 20 CDL). Analysis at the genus level showed that Blautia was detected significantly less often in the P group in both afferent limb (p=0.002) and pouch samples (p=0.008) compared to the other groups. Bacteroides and Sutterella were significantly less frequent among P and CDL groups in the pouch samples only (p=0.001 and 0.01 respectively). There was no significant difference in the proportions of these genera between outcome groups in the different batches. Conclusion: Differences in microbial composition are associated with outcomes following IPAA. Specifically, the genera Blautia, Bacteroides and Sutterella were found less frequently in patients with P and CDL compared to those without pouchitis. Further study may allow us to identify the role these organisms play in pouch pathogenesis, and to identify interactions occurring between microorganisms and host endogenous elements such as genotype and development of anti-microbial antibodies.