Dataset Information

Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis.

ABSTRACT: Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and unravel a distinct metabolite signature that separates affected individuals from controls nearly perfectly (AUC = 0.97). Individuals with MS are found to be depleted in butyrate-producing bacteria and in bacteria that produce indolelactate, an intermediate in generation of the potent neuroprotective antioxidant indolepropionate, which we found to be lower in their serum. We identify microbial and metabolite candidates that may contribute to MS and should be explored further for their causal role and therapeutic potential.

SUBMITTER: Levi I

PROVIDER: S-EPMC8080254 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis.

Levi Izhak I Gurevich Michael M Perlman Gal G Magalashvili David D Menascu Shay S Bar Noam N Godneva Anastasia A Zahavi Liron L Chermon Danyel D Kosower Noa N Wolf Bat Chen BC Malka Gal G Lotan-Pompan Maya M Weinberger Adina A Yirmiya Erez E Rothschild Daphna D Leviatan Sigal S Tsur Avishag A Didkin Maria M Dreyer Sapir S Eizikovitz Hen H Titngi Yamit Y Mayost Sue S Sonis Polina P Dolev Mark M Stern Yael Y Achiron Anat A Segal Eran E

Cell reports. Medicine 20210420 4

Multiple sclerosis (MS) is an immune-mediated disease whose precise etiology is unknown. Several studies found alterations in the microbiome of individuals with MS, but the mechanism by which it may affect MS is poorly understood. Here we analyze the microbiome of 129 individuals with MS and find that they harbor distinct microbial patterns compared with controls. To study the functional consequences of these differences, we measure levels of 1,251 serum metabolites in a subgroup of subjects and ...[more]

PMID: 33948576

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Project description:The objectives of this study are to examine the disparities in serum and intestinal tissue metabolites between a perimenopausal rat model and control rats and to analyze the diversity and functionality of intestinal microorganisms to determine the potential correlation between intestinal flora and metabolites. We established a rat model of perimenopausal syndrome (PMS) and performed an integrated analysis of metabolome and microbiome. Orthogonal partial least-squares discriminant analysis scores and replacement tests indicated distinct separations of anion and cation levels between serum and intestinal samples of the model and control groups. Furthermore, lipids and lipid-like molecules constituted the largest percentage of HMDB compounds in both serum and intestinal tissues, followed by organic acids and derivatives, and organoheterocyclic compounds, with other compounds showing significant variability. Moreover, analysis of diversity and functional enrichment of the intestinal microflora and correlation analysis with metabolites revealed significant variability in the composition of the intestinal flora between the normal control and perimenopausal groups, with these differentially expressed intestinal flora strongly correlated with their metabolites. The findings of this study are expected to contribute to understanding the indications and contraindications for estrogen application in perimenopausal women and to aid in the development of appropriate therapeutic agents.ImportanceIn this work, we employed 16S ribosomal RNA gene sequencing to analyze the gut microbes in stool samples. In addition, we conducted an ultra-high-performance liquid chromatography-tandem mass spectrometry-based metabolomics approach on gut tissue and serum obtained from rats with perimenopausal syndrome (PMS) and healthy controls. By characterizing the composition and metabolomic properties of gut microbes in PMS rats, we aim to enhance our understanding of their role in women's health, emphasizing the significance of regulating gut microbes in the context of menopausal women's well-being. We aim to provide a theoretical basis for the prevention and treatment of PMS in terms of gut microflora as well as metabolism.

Project description:Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system. Emerging evidence suggests the involvement of the microbiome and metabolic substances in the development of PDAC, yet the results remain contradictory. This study aims to identify the alterations and relationships in intratumoral microbiome and metabolites in PDAC. We collected matched tumor and normal adjacent tissue (NAT) samples from 105 PDAC patients and performed a 6-year follow-up. 2bRAD-M sequencing, untargeted liquid chromatography-tandem mass spectrometry, and untargeted gas chromatography-mass spectrometry were performed. Compared with NATs, microbial α-diversity decreased in PDAC tumors. The relative abundance of Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum was higher in PDAC tumor after adjusting for confounding factors body mass index and M stage, and the presence of Ralstonia pickettii_B was found associated with a worse overall survival. Metabolomic analysis revealed distinctive differences in composition between PDAC and NAT, with 553 discriminative metabolites identified. Differential metabolites were revealed to originate from the microbiota and showed significant interactions with shifted bacterial species through KO (KEGG Orthology) genes. These findings suggest that the PDAC microenvironment harbors unique microbial-derived enzymatic reactions, potentially influencing the occurrence and development of PDAC by modulating the levels of glycerol-3-phosphate, succinate, carbonate, and beta-alanine.ImportanceWe conducted a large sample-size pancreatic adenocarcinoma microbiome study using a novel microbiome sequencing method and two metabolomic assays. Two significant outcomes of our analysis are: (i) commensal opportunistic pathogens Staphylococcus aureus, Cutibacterium acnes, and Cutibacterium granulosum were enriched in pancreatic ductal adenocarcinoma (PDAC) tumors compared with normal adjacent tissues, and (ii) worse overall survival was found related to the presence of Ralstonia pickettii_B. Microbial species affect the tumorigenesis, metastasis, and prognosis of PDAC via unique microbe-enzyme-metabolite interaction. Thus, our study highlights the need for further investigation of the potential associations between pancreatic microbiota-derived omics signatures, which may drive the clinical transformation of microbiome-derived strategies toward therapy-targeted bacteria.

Dataset Information

Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis.

Publications

Potential role of indolelactate and butyrate in multiple sclerosis revealed by integrated microbiome-metabolome analysis.

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