Gut microbiota profiles in two New Zealand cohorts with overweight and prediabetes: a Tū Ora/PREVIEW comparative study.

Obesity-related metabolic diseases such as type 2 diabetes (T2D) are major global health issues, affecting hundreds of millions of people worldwide. The underlying factors are both diverse and complex, incorporating biological as well as cultural considerations. A role for ethnicity - a measure of self-perceived cultural affiliation which encompasses diet, lifestyle and genetic components - in susceptibility to metabolic diseases such as T2D is well established. For example, Asian populations may be disproportionally affected by the adverse 'TOFI' (Thin on the Outside, Fat on the Inside) profile, whereby outwardly lean individuals have increased susceptibility due to excess visceral and ectopic organ fat deposition. A potential link between the gut microbiota and metabolic disease has more recently come under consideration, yet our understanding of the interplay between ethnicity, the microbiota and T2D remains incomplete. We present here a 16S rRNA gene-based comparison of the fecal microbiota of European-ancestry and Chinese-ancestry cohorts with overweight and prediabetes, residing in New Zealand. The cohorts were matched for mean fasting plasma glucose (FPG: mean ± SD, European-ancestry: 6.1 ± 0.4; Chinese-ancestry: 6.0 ± 0.4 mmol/L), a consequence of which was a significantly higher mean body mass index in the European group (BMI: European-ancestry: 37.4 ± 6.8; Chinese-ancestry: 27.7 ± 4.0 kg/m; < 0.001). Our findings reveal significant microbiota differences between the two ethnicities, though we cannot determine the underpinning factors. In both cohorts was by far the dominant bacterial phylum (European-ancestry: 93.4 ± 5.5%; Chinese-ancestry: 79.6 ± 10.4% of 16S rRNA gene sequences), with and the next most abundant. Among the more abundant (≥1% overall relative sequence abundance) genus-level taxa, four zero-radius operational taxonomic units (zOTUs) were significantly higher in the European-ancestry cohort, namely members of the , , and genera. Differential abundance analysis further identified a number of additional zOTUs to be disproportionately overrepresented across the two ethnicities, with the majority of taxa exhibiting a higher abundance in the Chinese-ancestry cohort. Our findings underscore a potential influence of ethnicity on gut microbiota composition in the context of individuals with overweight and prediabetes.