Dissecting the role of the gut microbiota and diet on visceral fat mass accumulation

Abstract

Both gut microbiota and diet have been shown to impact visceral fat mass (VFM), a major risk factor for cardiometabolic disease, but their relative contribution has not been well characterised. We aimed to estimate and separate the effect of gut microbiota composition from that of nutrient intake on VFM in 1760 older female twins. Through pairwise association analyses, we identified 93 operational taxonomic units (OTUs) and 10 nutrients independently linked to VFM (FDR < 5%). Conditional analyses revealed that the majority (87%) of the 93 VFM-associated OTUs remained significantly associated with VFM irrespective of nutrient intake correction. In contrast, we observed that the effect of fibre, magnesium, biotin and vitamin E on VFM was partially mediated by OTUs. Moreover, we estimated that OTUs were more accurate predictors of VFM than nutrients and accounted for a larger percentage of its variance. Our results suggest that while the role of certain nutrients on VFM appears to depend on gut microbiota composition, specific gut microbes may affect host adiposity regardless of dietary intake. The findings imply that the gut microbiota may have a greater contribution towards shaping host VFM than diet alone. Thus, microbial-based therapy should be prioritised for VFM reduction in overweight and obese subjects.

Figure 1

VFM is strongly associated with gut microbiota composition and nutrient intake. (a) OTUs significantly associated with VFM using OTU as predictor of VFM and correcting for age, energy intake (kcal), and family structure. Red bars represent positive associations and green bars show negatives associations. (b) Dietary component associations with VFM and OTUs. Bubble plot represents the –log transformed p-value with negative associations (left side) and positive associations (right side) resulting from the prediction of VFM by each food component independently, correcting for age, energy intake (kcal), and family structure. The colour intensity represents the effect size, red representing positive associations and green showing negatives associations. The bar chart represents the number of significant (FDR < 5%) OTUs negatively (right) or positively (left) associated with each food component. The bars are coloured in relation to significance and direction of the association of OTUs with VFM: grey - not associated, red - positively associated, green - negatively associated. (c) Proportion of VFM-associated OTUs associated with one VFM-associated food component (dark blue), a non-VFM-associated food component (grey) or no food (light blue). (d) Potential mechanisms of action of diet and microbiota effects on host metabolism or VFM deposition. Four pathways are shown: (1) diet directly impacts the host without GM mediation (i.e. nitrogen, protein, cholesterol and tryptophan); (2) gut microbes (OTUs) directly impact VFM independent of the effect of diet; (3) microbes impact VFM and these effects can be modulated by diet; (4) dietary impacts on VFM require specific gut microbial composition.

Figure 2

Dietary impacts on VFM depend on gut microbiota composition, but the opposite trend does not apply. (a) Significance of the association between VFM and VFM-associated OTUs after correction for 5 nutrients. (b) Variation in the absolute effect size of OTUs on VFM, depending on dietary component adjustment; all results are at FDR < 5% unless noted by n.s. (not significant). (c) Significance of the association between VFM and dietary components after correcting for VFM-associated OTUs relative abundance. (d) Significance of association between VFM and 93 OTUs represented as –log(P-value) while correcting for different dietary components.

Figure 3

OTUs mediate the effects of nutrients on VFM. (a) OTU mediation of fibre and vitamin E on VFM. In each model the left box represents the causal variable (the nutrient), the top box is the mediator (OTUs, 1^st PC for the OTUs listed for each nutrient in Supplementary Table 6) and the right box is the response (VFM). The number by the top arrow represents the average causal mediation effect (ACME) and the one on the bottom arrow is the average direct effect (ADE). The number under the VFM box the percentage of mediation. *P < 0.05, **P < 0.01, ***P < 0.001. (b) Proportion of VFM variance attributed to OTUs and nutrients (R²) in a linear model.