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Altered Fecal Metabolites and Colonic Glycerophospholipids Were Associated With Abnormal Composition of Gut Microbiota in a Depression Model of Mice.

ABSTRACT: The microbiota-gut-brain axis has been considered to play an important role in the development of depression, but the underlying mechanism remains unclear. The gastrointestinal tract is home to trillions of microbiota and the colon is considered an important site for the interaction between microbiota and host, but few studies have been conducted to evaluate the alterations in the colon. Accordingly, in this study, we established a chronic social defeated stress (CSDS) mice model of depression. We applied 16S rRNA gene sequencing to assess the gut microbial composition and gas and liquid chromatography-mass spectroscopy to identify fecal metabolites and colonic lipids, respectively. Meanwhile, we used Spearman's correlation analysis method to evaluate the associations between the gut microbiota, fecal metabolites, colonic lipids, and behavioral index. In total, there were 20 bacterial taxa and 18 bacterial taxa significantly increased and decreased, respectively, in the CSDS mice. Further, microbial functional prediction demonstrated a disturbance of lipid, carbohydrate, and amino acid metabolism in the CSDS mice. We also found 20 differential fecal metabolites and 36 differential colonic lipids (in the category of glycerolipids, glycerophospholipids, and sphingolipids) in the CSDS mice. Moreover, correlation analysis showed that fecal metabolomic signature was associated with the alterations in the gut microbiota composition and colonic lipidomic profile. Of note, three lipids [PC(16:0/20:4), PG(22:6/22:6), and PI(18:0/20:3), all in the category of glycerophospholipids] were significantly associated with anxiety- and depression-like phenotypes in mice. Taken together, our results indicated that the gut microbiota might be involved in the pathogenesis of depression via influencing fecal metabolites and colonic glycerophospholipid metabolism.

SUBMITTER: Gong X

PROVIDER: S-EPMC8326978 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:ObjectiveFrailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome.MethodsWe collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers.ResultsOlder adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman's correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability.ConclusionsFrailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.

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Altered Fecal Metabolites and Colonic Glycerophospholipids Were Associated With Abnormal Composition of Gut Microbiota in a Depression Model of Mice.

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