| Summary: | Refined foods are commonly depleted in certain bioactive components that are abundant in ‘natural’ (plant) foods. Identification and addition of these ‘missing’ bioactives in the diet is, therefore, necessary to counteract the deleterious impact of convenience food. In this study, multiomics approaches were employed to assess the addition of the popular supplementary soluble dietary fibers inulin and psyllium, both in isolation and in combination with a refined animal feed. A 16S rRNA sequencing and <sup>1</sup>H NMR metabolomic investigation revealed that, whilst inulin mediated an increase in <i>Bifidobacteria</i>, psyllium elicited a broader microbial shift, with <i>Parasutterella</i> and <i>Akkermansia</i> being increased and <i>Enterorhabdus</i> and <i>Odoribacter</i> decreased. Interestingly, the combination diet benefited from both inulin and psyllium related microbial changes. Psyllium mediated microbial changes correlated with a reduction of glucose (R −0.67, −0.73, respectively, <i>p</i> < 0.05) and type 2 diabetes associated metabolites: 3-methyl-2-oxovaleric acid (R −0.72, −0.78, respectively, <i>p</i> < 0.05), and citrulline (R −0.77, −0.71, respectively, <i>p</i> < 0.05). This was in line with intestinal and hepatic carbohydrate response (e.g., <i>Slc2a2</i>, <i>Slc2a5</i>, <i>Khk</i> and <i>Fbp1</i>) and hepatic lipogenesis (e.g., <i>Srebf1</i> and <i>Fasn</i>), which were significantly reduced under psyllium addition. Although established in the liver, the intestinal response associated with psyllium was absent in the combination diet, placing greater significance upon the established microbial, and subsequent metabolomic, shift. Our results therefore highlight the heterogeneity that exists between distinct dietary fibers in the context of carbohydrate uptake and metabolism, and supports psyllium containing combination diets, for their ability to negate the impact of a refined diet.
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