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The unique composition of Indian gut microbiome, gene catalogue and associated faecal metabolome deciphered using multi-omics approaches

ABSTRACT: BACKGROUND: Metagenomic studies carried out in the past decade have led to an enhanced understanding of the gut microbiome in human health, however, the Indian gut microbiome is not well explored yet. We analysed the gut microbiome of 110 healthy individuals from two distinct locations (North-Central and Southern) in India using multi-omics approaches, including 16S rRNA gene amplicon sequencing, whole genome shotgun metagenomic sequencing, and metabolomic profiling of faecal and serum samples.
RESULTS: The gene catalogue established in this study emphasizes the uniqueness of the Indian gut microbiome in comparison to other populations. The gut microbiome of the cohort from North-Central India, which was primarily consuming a plant-based diet, was found to be associated with Prevotella, and also showed an enrichment of Branched Chain Amino Acid (BCAA) and lipopolysaccharide (LPS) biosynthesis pathways. In contrast, the gut microbiome of the cohort from Southern India, which was consuming an omnivorous diet, showed associations with Bacteroides, Ruminococcus and Faecalibacterium, and had an enrichment of Short Chain Fatty Acid (SCFA) biosynthesis pathway and BCAA transporters. This corroborated well with the metabolomics results, which showed higher concentration of BCAAs in the serum metabolome of the North-Central cohort and an association with Prevotella. In contrast, the concentration of BCAAs were found higher in the faecal metabolome of the Southern-India cohort, and showed a positive correlation with the higher abundance of BCAA transporters.
CONCLUSIONS: The study reveals the unique composition of Indian gut microbiome, establishes the Indian gut microbial gene catalogue, and compares it with the gut microbiome of other populations. The functional associations revealed using metagenomic and metabolomic approaches provide novel insights on the gut-microbe-metabolic axis, which will be useful for future epidemiological and translational researches.

INSTRUMENT(S): Gas Chromatography MS - Positive (GC-MS (Positive))

SUBMITTER: Darshan Dhakan

PROVIDER: MTBLS803 | MetaboLights | 2019-01-04

REPOSITORIES: MetaboLights

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Project description:The current treatment for Celiac Disease (CD) is adhering to a gluten-free diet (GFD), although its long-term molecular effects are still undescribed. New molecular features detectable in faecal samples may improve and facilitate non-invasive clinical management of CD on GFD. For this purpose, faecal small non-coding RNAs (sncRNAs) and gut microbiome profiles were concomitantly explored in CD subjects in relation to strict (or not) GFD adherence over time. In the present observational study, we performed small RNA and shotgun metagenomic sequencing in stool from 63 treated CD (tCD) subjects and 66 sex- and age-matched healthy controls. tCD included 51 individuals on strict GFD and with negative transglutaminase (TG) serology (tCD-TG-) and 12 symptomatic with not strict/short-time of GFD adherence and positive TG serology (tCD-TG+). Samples from additional 40 adult healthy individuals and from a cohort of 19 untreated paediatric CD subjects and 19 sex/age matched controls were analyzed to further test the outcomes. Several miRNA, other sncRNA (piRNA and tRNA) and microbiota profiles were altered in tCD subjects(adj.p<0.05). Findings were validated in one external group of controls. In tCD-TG-, GFD duration correlated with five miRNA levels (p<0.05): for miR-4533-3p and miR-2681-3p, the longer the diet adherence, the less the expression differed from controls. tCD-TG+ and untreated paediatric CD patients showed a similar miRNA dysregulation. Immune-response, trans-membrane transport and cell death pathways were enriched in targets of identified miRNAs. Bifidobacterium longum, Ruminococcus bicirculans and Haemophilus parainfluenzae abundances shifted (adj. p<0.05) with a progressive reduction of denitrification pathways with GFD length. Integrative analysis highlighted 121 miRNA-bacterial relationships (adj.p<0.05). Specific faecal sncRNA and microbial patterns characterise CD subjects on GFD, reflecting either the long-term effects or the gut inflammatory status, in case of a not strict/short-time adherence. Our findings suggest novel host-microbial interplays and could help the discovery of biomarkers for the clinical monitoring of GFD over time.

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The unique composition of Indian gut microbiome, gene catalogue and associated faecal metabolome deciphered using multi-omics approaches

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