Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice
ABSTRACT: Exposure to environmental chemicals during windows of development is a potentially contributing factor in gut microbiota dysbiosis, and linked to chronic diseases and developmental disorders. We used a community-level model of microbiota metabolism to investigate the effects of diethylhexyl phthalate (DEHP), a ubiquitous plasticizer implicated in neurodevelopmental disorders, on the composition and metabolite outputs of gut microbiota in young mice. Administration of DEHP by oral gavage increased the abundance of Lachnoclostridum, while decreasing Akkermansia, Odoribacter, and Clostridium sensu stricto. Addition of DEHP to in vitro cultured cecal microbiota increased the abundance of Alistipes, Paenibacillus, and Lachnoclostridium. Untargeted metabolomics showed that DEHP broadly altered the metabolite profile in the culture. Notably, DEHP enhanced the production of p-cresol, while inhibiting butyrate synthesis. Metabolic model-guided correlation analysis indicated that the likely sources of p-cresol are Clostridium species. Our results suggest that DEHP can directly modify the microbiota to affect production of bacterial metabolites linked with neurodevelopmental disorders.
INSTRUMENT(S): Liquid Chromatography MS - Negative (LC-MS (Negative)), Liquid Chromatography MS - Positive (LC-MS (Positive))
Project description:Uncovering the phylogenetic composition of microbial community and the potential functional capacity of microbiome in different gut locations is of great importance to pig production. Here we performed a comparative analysis of gut microbiota and metagenomics among jejunum, ileum and cecum in pigs with distinct fatness. 16S rRNA gene sequencing revealed dramatic differences of microbial composition, diversity and species abundance between small intestine and cecum. Clostridium and SMB53 were enriched in the small intestine, while Prevotella, Treponema, Ruminococcus and Faecalibacterium showed a higher abundance in the cecum. Functional capacity analysis of gut microbiome revealed that the microbiome of small intestine plays important roles in the metabolism of small molecule nutrients, while the microbiome of cecum has the stronger ability to degrade xylan, pectin and cellulose. We identified tens of fatness associated-bacterial species including Escherichia spp. that showed a notable increase of relative abundance in all three gut locations of high fatness pigs. We further suggested that the potential pathogens, inflammation process, and microbial metabolism and nutrient sensing are involved in the high fatness of pigs. These results improve our knowledge about microbiota compositions in different gut locations, and give an insight into the effect of gut microbiota on porcine fatness.
Project description:Growing evidence shows that neuropsychiatric disorders, such as depression, are linked with gut microbiome through the gut-brain axis. Cistanches Herba is well known for the treatment of "kidney-yang" deficiency in traditional Chinese medicine (TCM), and has been used for treatment of neurodegenerative diseases in recent years. In this study, chronic unpredictable stress (CUS)-induced depression model was established to explore the impact of Cistanche tubulosa extract (CTE) on behavioral tests, monoamine neurotransmitters and neurotrophic factors in hippocampus and colon, gut microbiota composition, and short-chain fatty acids (SCFAs) production. Moreover, correlation analysis was used to evaluate the functional relationship between altered gut microbiota, changed neurotransmitters and neurotrophins in hippocampus and colon, and disturbed concentration of SCFAs. CTE significantly improved depression-like behaviors in rats under CUS. Brain level of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) expression in CUS rats were restored by CTE. The relative abundance of gut microbiota and the concentrations of acetate and hexanoic acid could also be modulated by CTE treatment. We further showed that the application of CTE in CUS rats led to strong correlation among disrupted gut microbiota composition, hippocampus neurotransmitter levels, and production of neuroactive metabolite SCFAs. Altogether, these results identify CTE as a potential treatment for depressive symptoms by restoring homeostasis of gut microbiota for microbiota-gut-brain axis disorders, opening new avenues in the field of neuropsychopharmacology.
Project description:BACKGROUND:Roux-en-Y gastric bypass (RYGB) surgery is a last-resort treatment to induce substantial and sustained weight loss in cases of severe obesity. This anatomical rearrangement affects the intestinal microbiota, but so far, little information is available on how it interferes with microbial functionality and microbial-host interactions independently of weight loss. METHODS:A rat model was employed where the RYGB-surgery cohort is compared to sham-operated controls which were kept at a matched body weight by food restriction. We investigated the microbial taxonomy and functional activity using 16S rRNA amplicon gene sequencing, metaproteomics, and metabolomics on samples collected from theileum, the cecum, and the colon, and separately analysed the lumen and mucus-associated microbiota. RESULTS:Altered gut architecture in RYGB increased the relative occurrence of Actinobacteria, especially Bifidobacteriaceae and Proteobacteria, while in general, Firmicutes were decreased although Streptococcaceae and Clostridium perfringens were observed at relative higher abundances independent of weight loss. A decrease of conjugated and secondary bile acids was observed in the RYGB-gut lumen. The arginine biosynthesis pathway in the microbiota was altered, as indicated by the changes in the abundance of upstream metabolites and enzymes, resulting in lower levels of arginine and higher levels of aspartate in the colon after RYGB. CONCLUSION:The anatomical rearrangement in RYGB affects microbiota composition and functionality as well as changes in amino acid and bile acid metabolism independently of weight loss. The shift in the taxonomic structure of the microbiota after RYGB may be mediated by the resulting change in the composition of the bile acid pool in the gut and by changes in the composition of nutrients in the gut. Video abstract.
Project description:<h4>Background</h4>Recent evidence suggests that the gut microbiota is an important contributing factor to obesity and obesity related metabolic disorders, known as the metabolic syndrome. The aim of this study was to characterise the intestinal microbiota in two pig models of obesity namely Göttingen minipigs and the Ossabaw minipigs.<h4>Methods and findings</h4>The cecal, ileal and colonic microbiota from lean and obese Osabaw and Göttingen minipigs were investigated by Illumina-based sequencing and by high throughput qPCR, targeting the 16S rRNA gene in different phylogenetic groups of bacteria. The weight gain through the study was significant in obese Göttingen and Ossabaw minipigs. The lean Göttingen minipigs' cecal microbiota contained significantly higher abundance of Firmicutes (P<0.006), Akkermensia (P<0.01) and Methanovibribacter (P<0.01) than obese Göttingen minipigs. The obese Göttingen cecum had higher abundances of the phyla Spirochaetes (P<0.03), Tenericutes (P<0.004), Verrucomicrobia (P<0.005) and the genus Bacteroides (P<0.001) compared to lean minipigs. The relative proportion of Clostridium cluster XIV was 7.6-fold higher in cecal microbiota of obese Göttingen minipigs as compared to lean. Obese Ossabaw minipigs had a higher abundance of Firmicutes in terminal ileum and lower abundance of Bacteroidetes in colon than lean Ossabaw minipigs (P<0.01). Obese Ossabaws had significantly lower abundances of the genera Prevotella and Lactobacillus and higher abundance of Clostridium in their colon than the lean Ossabaws. Overall, the Göttingen and Ossabaw minipigs displayed different microbial communities in response to diet-induced obesity in the different sections of their intestine.<h4>Conclusion</h4>Obesity-related changes in the composition of the gut microbiota were found in lean versus obese Göttingen and Ossabaw minipigs. In both pig models diet seems to be the defining factor that shapes the gut microbiota as observed by changes in different bacteria divisions between lean and obese minipigs.
Project description:Early gut microbial colonization is important for postnatal metabolic and immune development. However, little is known about the effects of different feeding modes (suckling versus bottle-feeding) or microbial sources on this process in farm animals. We found that suckled and bottle-fed newborn lambs had their own distinct gut microbiota. Results from 16S rRNA gene sequencing and qPCR showed that, compared with suckling, bottle feeding significantly increased the abundances of Escherichia/Shigella, Butyricicoccus, and Clostridium XlVa, while significantly decreased the abundance of Clostridium XI. The higher levels of Escherichia/Shigella in bottle-fed lambs suggest that artificial feeding may increase the number of potential pathogens and delay the establishment of the anaerobic environment and anaerobic microbes. Feeding modes also affected the direct transmission of bacteria from the mother and the environment to newborns. The SourceTracker analysis estimated that the early gut microbes of suckled lambs were mainly derived from the mother's teats (43%) and ambient air (28%); whereas those of bottle-fed lambs were dominated by bacteria from the mother's vagina (46%), ambient air (31%), and the sheep pen floor (12%). These findings advance our understanding of gut microbiota in early life and may help design techniques to improve gut microbiota and health.
Project description:Recent studies underscore important roles of intestinal microbiota and the bacterial lipopolysaccharides (LPS) production in the pathogenesis of liver disease. However, how gut microbiota alters in response to the development of steatosis and subsequent progression to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains unclear. We aimed to study the gut microbial changes over liver disease progression using a streptozotocin-high fat diet (STZ-HFD) induced NASH-HCC C57BL/6J mouse model that is highly relevant to human liver disease. The fecal microbiota at various liver pathological stages was analyzed by 16S rDNA gene pyrosequencing. Both UniFrac analysis and partial least squares-discriminant analysis showed significant structural alterations in gut microbiota during the development of liver disease. Co-abundance network analysis highlighted relationships between genera. Spearman correlation analysis revealed that the bacterial species, Atopobium spp., Bacteroides spp., Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis, Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp., markedly increased in model mice, were positively correlated with LPS levels and pathophysiological features. Taken together, the results showed that the gut microbiota was altered significantly in the progression of liver disease. The connection between the gut microbial ecology and the liver pathology may represent potential targets for the prevention and treatment of chronic liver disease and HCC.
Project description:Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
Project description:Polysaccharides from morels possess many characteristics beneficial to health, such as anti-tumor and immunomodulatory activities. The gut microbiota plays a critical role in the modulation of immune function. However, the impact of morel polysaccharides on the gut microbiota has not yet been explored. In this study, a high-throughput pyrosequencing technique was used to investigate the effects of MP, a new heteropolysaccharide extracted from wild morels, on the diversity and composition of microbiota along the intestine in mice, as well as the production of short-chain fatty acids (SCFAs). The results showed that MP treatment increased the number of operational taxonomic unit (OTUs) and diversity along the intestine, especially in the small intestine. MP treatment induced a significant decrease in the number of Firmicutes and a significant increase in the number of Bacteroidetes in the small intestine microbiota. It was also observed that the relative abundance of SCFA-producing bacteria, especially Lachnospiraceae, was increased in both the cecum and colon of MP-treated mice. Moreover, MP promoted the production of SCFAs in mice. These results provide a foundation for further understanding the health benefits conferred by morel polysaccharides.
Project description:Cumulative evidence shows a linkage between gut microbiota pattern and depression through the brain-gut microbiome axis. The aim of this systematic review was to identify the alterations of the gut microbiota patterns in people with depression compared to healthy controls. A comprehensive literature search of human studies, published between January 2000 and June 2019, was reviewed. The key words included gastrointestinal microbiome, gut microbiome, microbiota, depression, depressive symptoms, and depressive disorder. The systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles met the eligibility criteria. Disparities in ?-diversity and ?-diversity of the microbiota existed in people with depression compared to healthy controls. At the phylum level, there were inconsistencies in the abundance of Firmicutes, Bacteroidetes, and Proteobacteria. However, high abundance in Actinobacteria and Fusobacteria phyla were observed in people with depression. On the family level, high abundance of Actinomycineae, Coriobacterineae, Bifidobacteriaceae, Clostridiales incertae sedis XI, Porphyromonadaceae, Clostridiaceae, Lactobacillaceae, Streptococcaceae, Eubacteriaceae, Thermoanaerobacteriaceae, Fusobacteriaceae, Nocardiaceae, Streptomycetaceae, and low abundance of Veillonellaceae, Prevotellaceae, Bacteroidaceae, Sutterellaceae, Oscillospiraceae, Marniabilaceae, and Chitinophagaceae were observed in people with depression. On the genus level, high abundance of Oscillibacter, Blautia, Holdemania, Clostridium XIX, Anaerostipes, Anaerofilum, Streptococcus, Gelria, Turicibacter, Parabacteroides, Eggerthella, Klebsiella, Paraprevotella, Veillonella, Clostridium IV, Erysipelotrichaceae incertae sedis, Eubacterium, Parvimonas, Desulfovibrio, Parasutterella, Actinomyces, Asaccharobacter, Atopobium, Olsenella and low abundance of Coprococcus, Lactobacillus, Escherichia/Shigella, Clostridium XlVa, Dialister, Howardella, Pyramidobacter, and Sutterella were found in people with depression. Alteration of gut microbiome patterns was evident in people with depression. Further evidence is warranted to allow for the translation of microbiome findings toward innovative clinical strategies that may improve treatment outcomes in people with depression.
Project description:Human intestinal microbiota plays a number of important roles in human health and is also implicated in several gastrointestinal disorders. Although the diversity of human gut microbiota in adults and in young children has been examined, few reports of microbiota composition are available for adolescents. In this work, we used Microbiota Array for high-throughput analysis of distal gut microbiota in adolescent children 11-18 years of age. Samples obtained from healthy adults were used for comparison. Adolescent and adult groups could be separated in the principal components analysis space based on the relative species abundance of their distal gut microbiota. All samples were dominated by class Clostridia. A core microbiome of 46 species that were detected in all examined samples was established; members of genera Ruminococcus, Faecalibacterium, and Roseburia were well represented among core species. Comparison of intestinal microbiota composition between adolescents and adults revealed a statistically significantly higher abundance of genera Bifidobacterium and Clostridium among adolescent samples. The number of detected species was similar between sample groups, indicating that it was the relative abundances of the genera and not the presence or absence of a specific genus that differentiated adolescent and adult samples. In summary, contrary to the current belief, this study suggests that the gut microbiome of adolescent children is different from that of adults.