Project description:Celiac disease (CD) is an autoimmune small bowel disease. The pattern of gut microbiota is closely related to dietary habits, genetic background, and geographical factors. There is a lack of research on CD-related gut microbiota in China. This study aimed to use 16S rDNA sequencing and metabolomics to analyze the fecal microbial composition and metabolome characteristics in patients diagnosed with CD in Northwest China, and to screen potential biomarkers that could be used for its diagnosis. A significant difference in the gut microbiota composition was observed between the CD and healthy controls groups. At the genus level, the abundance of Streptococcus, Lactobacillus, Veillonella, and Allisonella communities in the CD group were increased (Q < 0.05). Furthermore, the abundance of Ruminococcus, Faecalibacterium, Blautia, Gemmiger, and Anaerostipes community in this group were decreased (Q < 0.05). A total of 222 different fecal metabolites were identified in the two groups, suggesting that CD patients have a one-carbon metabolism defect. Four species of bacteria and six metabolites were selected as potential biomarkers using a random forest model. Correlation analysis showed that changes in the gut microbiota were significantly correlated with changes in fecal metabolite levels. In conclusion, the patterns of distribution of gut microbiota and metabolomics in patients with CD in Northwest China were found to be unique to these individuals. This has opened up a new way to explore potential beneficial effects of supplementing specific nutrients and potential diagnostic and therapeutic targets in the future.
Project description:Physical exercise can produce changes in the microbiota, conferring health benefits through mechanisms that are not fully understood. We sought to determine the changes driven by exercise on the gut microbiota and on the serum and fecal metabolome using 16S rRNA gene analysis and untargeted metabolomics. A total of 85 serum and 12 fecal metabolites and six bacterial taxa (Romboutsia, Escherichia coli TOP498, Ruminococcaceae UCG-005, Blautia, Ruminiclostridium 9 and Clostridium phoceensis) were modified following a controlled acute exercise session. Among the bacterial taxa, Ruminiclostridium 9 was the most influenced by fecal and serum metabolites, as revealed by linear multivariate regression analysis. Exercise significantly increased the fecal ammonia content. Functional analysis revealed that alanine, aspartate and glutamate metabolism and the arginine and aminoacyl-tRNA biosynthesis pathways were the most relevant modified pathways in serum, whereas the phenylalanine, tyrosine and tryptophan biosynthesis pathway was the most relevant pathway modified in feces. Correlation analysis between fecal and serum metabolites suggested an exchange of metabolites between both compartments. Thus, the performance of a single exercise bout in cross-country non-professional athletes produces significant changes in the microbiota and in the serum and fecal metabolome, which may have health implications.
Project description:Compared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets - especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis. In total, 368 stool samples from 38 different animal species, including Homo sapiens, belonging to four diverse mammalian orders were collected at seven different locations and analyzed by 16S rRNA gene amplicon sequencing. Comprehensive data analysis was performed to (i) determine the overall impact of host phylogeny vs. diet, location, and ecology and to (ii) examine the general pattern of fecal bacterial diversity across captive mammals and humans.By using a controlled study design with captive mammals we could verify that host phylogeny is the most dominant driver of mammalian gut microbiota composition. However, the effect of ecology appears to be able to overcome host phylogeny and should therefore be studied in more detail in future studies. Most importantly, our study could observe a remarkable decrease of Spirochaetes and Prevotella in westernized humans and platyrrhines, which is probably not only due to diet, but also to the social behavior and structure in these communities.Our study highlights the importance of phylogenetic relationship and ecology within the evolution of mammalian fecal microbiota composition. Particularly, the observed decrease of Spirochaetes and Prevotella in westernized communities might be associated to lifestyle dependent rapid evolutionary changes, potentially involved in the establishment of dysbiotic microbiomes, which promote the etiology of chronic diseases.
Project description:Gut microbiome plays an essential role in modulating host immune responses. However, little is known about the interaction of microbiota, their metabolites and relevant inflammatory responses in the gut. By treating the mice with three different antibiotics (enrofloxacin, vancomycin, and polymixin B sulfate), we aimed to investigate the effects of different antibiotics exposure on gut microbiota, microbial metabolism, inflammation responses in the gut, and most importantly, pinpoint the underlying interactions between them. Although the administration of different antibiotics can lead to different effects on mouse models, the treatment did not affect the average body weight of the mice. A heavier caecum was observed in vancomycin treated mice. Treatment by these three antibiotics significantly up-regulated gene expression of various cytokines in the colon. Enrofloxacin treated mice seemed to have an increased Th1 response in the colon. However, such a difference was not found in mice treated by vancomycin or polymixin B sulfate. Vancomycin treatment induced significant changes in bacterial composition at phylum and family level and decreased richness and diversity at species level. Enrofloxacin treatment only induced changes in composition at family presenting as an increase in Prevotellaceae and Rikenellaceae and a decrease in Bacteroidaceae. However, no significant difference was observed after polymixin B sulfate treatment. When compared with the control group, significant metabolic shift was found in the enrofloxacin and vancomycin treated group. The metabolic changes mainly occurred in Valine, leucine, and isoleucine biosynthesis pathway and beta-Alanine metabolism in enrofloxacin treated group. For vancomycin treatment metabolic changes were mainly found in beta-Alanine metabolism and Alanine, aspartate and glutamate metabolism pathway. Moreover, modifications observed in the microbiota compositions were correlated with the metabolite concentrations. For example, concentration of pentadecanoic acid was positively correlated with richness of Rikenellaceae and Prevotellaceae and negatively correlated with Enterobacteriaceae. This study suggests that the antibiotic-induced changes in gut microbiota might contribute to the inflammation responses through the alternation of metabolic status, providing a novel insight regarding a complex network that integrates the different interactions between gut microbiota, metabolic functions, and immune responses in host.
Project description:Fecal microbiota transplantation (FMT) and probiotics therapies represent key clinical options, yet their complex effects on the host are not fully understood. We evaluated the comprehensive effects of FMT using diarrheal or normal feces, as well as probiotic therapies, on multiple anatomical sites in healthy cynomolgus macaques through colonoscopy and surgery. Our research revealed that FMT led to a partial microbiome transplantation without exhibiting the donor's fecal clinical characteristics. Notably, FMT increased insulin and C-peptide levels in each animal according time series, regardless of fecal conditions. Immunologically, a reduction in neutrophil-to-lymphocyte ratio were exclusively observed in femoral veins of FMT group. In blood chemistry analyses, reductions in aspartate aminotransferase, blood urea nitrogen, and creatinine were observed in the femoral veins, while elevated levels of alanine aminotransferase and calcium were exclusively detected in the portal veins. These changes were not observed in the probiotic group. Also, short chain fatty acids were significantly higher increase in portal veins rather than femoral veins. Transcriptome analysis of liver tissues showed that metabolic pathways were primarily affected by both FMT and probiotics therapies. In summary, FMT therapy significantly influenced metabolic, immunologic and transcriptomic responses in normal macaque models, regardless of fecal conditions. Also, these macaque models, which utilize surgery and colonoscopy, serve as a human-like preclinical platform for evaluating long-term effects and anatomically specific responses to gut-targeted interventions, without the need for animal sacrifice.
Project description:BackgroundChronic kidney disease (CKD) is a severe public health problem associated with a disordered gut microbiome. However, the functional alterations of microbiota and their cross talk with metabolism pathways based on disease severity remain unclear.ResultsWe performed metagenomics and untargeted metabolomics in a cohort of 68 patients with CKD of differing severities and 20 healthy controls to characterize the complex interplay between the gut microbiome and fecal and serum metabolites during CKD progression. We identified 26 microbial species that significantly changed in patients with CKD; 18 species changed as the disease progressed, and eight species changed only in a specific CKD group. These distinct changes in gut microbiota were accompanied by functional alterations in arginine and proline, arachidonic acid, and glutathione metabolism and ubiquinone and other terpenoid-quinone biosynthesis pathways during CKD progression. Further metabolomic analyses revealed that the distributions of toxic and pro-oxidant metabolites from these four essential metabolic pathways varied in the feces and serum as CKD progressed. Furthermore, we observed a complex co-occurrence between CKD severity-related bacteria and the characterized metabolites from the four essential metabolic pathways. Notably, Ruminococcus bromii, fecal hydroquinone, and serum creatinine were identified as the main contributors to the integrated network, indicating their key roles in CKD progression. Moreover, a noninvasive model including R. bromii and fecal hydroquinone, L-cystine, and 12-keto-tetrahydro-LTB4 levels classified the CKD severity (area under the curve [AUC]: > 0.9) and had better performance than the serum creatinine level for mild CKD (AUC: 0.972 vs. 0.896).ConclusionsPerturbed CKD severity-related gut microbiota may contribute to unbalanced toxic and pro-oxidant metabolism in the gut and host, accelerating CKD progression, which may be an early diagnostic and therapeutic target for CKD. Video Abstract.
Project description:Methylphenidate is one of the most widely used oral treatments for attention-deficit/hyperactivity disorder (ADHD). The drug is mainly absorbed in the small intestine and has low bioavailability. Accordingly, a high interindividual variability in terms of response to the treatment is known among ADHD patients treated with methylphenidate. Nonetheless, very little is known about the factors that influence the drug's absorption and bioavailability. Gut microbiota has been shown to reduce the bioavailability of a wide variety of orally administered drugs. Here, we tested the ability of small intestinal bacteria to metabolize methylphenidate. In silico analysis identified several small intestinal bacteria to harbor homologues of the human carboxylesterase 1 enzyme responsible for the hydrolysis of methylphenidate in the liver into the inactive form, ritalinic acid. Despite our initial results hinting towards possible bacterial hydrolysis of the drug, up to 60% of methylphenidate is spontaneously hydrolyzed in the absence of bacteria and this hydrolysis is pH-dependent. Overall, our results indicate that the stability of methylphenidate is compromised under certain pH conditions in the presence or absence of gut microbiota.
Project description:IntroductionThe Asian elephant (Elephas maximus) is a giant herbivore classified as an endangered wildlife species by the International Union for Conservation of Threatened Species.This study aims to investigate and compare the core gut microbiota of captive Asian elephants from three different locations in Yunnan Province, China, to explore the impact of environmental and husbandry factors on microbial diversity.MethodsWe collected fecal samples from 29 captive Asian elephants from three locations and performed full-length 16S rRNA gene sequencing. Microbial diversity was assessed using alpha diversity (Chao1 and Shannon indexes) and beta diversity (Bray-Curtis and Euclidean distance metrics). Principal coordinate analysis (PCoA) was used to visualize microbial variation among groups.ResultsAlpha diversity analysis showed that the microbial diversity in the Yexianggu group was higher than that in the other groups. Bray-Curtis and Euclidean metrics revealed significant differences among the microbial communities. Bacteroidetes and Firmicutes, which are key cellulose-degrading bacteria, were the dominant phyla in all groups. Synergistaceae was the most abundant family in the Menghai group, while Lachnospiraceae and Pirellulaceae were more abundant in the Yexianggu and Yuantongshan groups, respectively. Genus p-1008-a5-gut-group was more abundant in Yexianggu, and Prevotella was predominant in Menghai.DiscussionThese results indicate that habitat and husbandry practices significantly influence the gut microbiota of captive Asian elephants. The identification of bacterial species such as Lactobacillus fermentum, Clostridium neonatale, Enterococcus mundtii, Klebsiella huaxiensis, Corynebacterium nasicanis, and Streptococcus equinus highlights the potential role of specific microbes in maintaining host-microbial interactions. Promoting microbial diversity through improved captive conditions could enhance the health of these endangered animals.
Project description:Stress gene expression profiling of hepatic tissue in wild caught juvenile coho from perenial streams. Stream locations were based on a gradient of urban impact
Project description:BackgroundOsteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients.MethodsFecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed.ResultsThe OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing.ConclusionOur study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.