Title:

Functional Potential of the Gut Microbiome in NH Bhutanese Refugee Adults with Glycemic Impairment

Objectives: To assess the relationship between the functional potential of the fecal microbiota, diet, and glycemic status in Bhutanese refugee adults residing in New Hampshire. We hypothesized that functional richness would be lower in type 2 diabetes (T2D) and would correlate with diet. Methods: This was a cross-sectional study of Bhutanese refugee adults (n=50) in NH. The functional potential of fecal microbial communities was quantified by shallow shotgun sequencing and subsequent protein mapping with the PALADIN pipeline. Functional richness was determined by summing the unique number of UniProt IDs identified in each sample and compared according to T2D status (Wilcoxon rank sum test). Spearman correlations were used to examine relationships between functional richness, diet, and glycemic status. Results: There was a high prevalence of overweight or obesity (92%) and type 2 diabetes (42%). Although our previous work showed significantly lower compositional richness in T2D (i.e., number of taxonomic groups per sample), and functional richness was correlated to compositional richness after adjusting for sequencing depth (rho=0.795 p<0.0001), functional richness was not significantly different according to T2D status (median [IQR]: 157,504 [38,977] UniProt IDs for non-T2D and 129,709 [47,837] UniProt IDs for T2D, p=0.140). Additionally, functional richness was not correlated to glycemic status (glycated hemoglobin, fasting plasma glucose, HOMA-IR) or dietary intake (Healthy Eating Index score, total fiber). Conclusions: Functional richness was correlated with compositional richness but did not differ by T2D. Future analyses will involve gene set enrichment to ascertain any specific functional characteristics or pathways that differ according to T2D status. This analysis will provide a greater understanding of the mechanisms tying the gut microbiota to glycemic impairment, beyond compositional characterizations, particularly in an underrepresented population that experiences a large burden of chronic disease. Funding Sources: Institutional Development Award from the NIH National Institute of General Medical Sciences (P20GM113131) and USDA National Institute of Food and Agriculture Hatch Project (NH00688).

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