Attenuation of colitis-related metabolic dysregulation via consumption of wholemeal sourdough bread but not wholemeal bread: a molecular discovery.

Epidemiological studies reveal that the majority of adult patients with inflammatory bowel disease (IBD) are obese and/or overweight. Whole wheat sourdough produced by lactic acid bacterial (LAB) fermentation can provide numerous benefits. In this study, the potential therapeutic effects of consuming whole wheat sourdough bread (singly fermented by two high-metabolite-producing LAB strains, Lactobacillus crustorum (LC) or Lactobacillus fermentum (LF)) on colon and liver metabolic function in an obese (high-fat diet) and ulcerative colitis (5% dextran sulfate sodium, DSS) induced male rat model were investigated, and the underlying mechanisms were investigated via multi-omics approaches. The results showed that compared to the obesity-colitis model (OC), intake of whole wheat sourdough bread diets rather than wheat bread (WB) or whole wheat bread (WW) effectively restored liver morphology, normalized colon length, and lowered colonic oxidative stress by reducing the levels of malondialdehyde (MDA) and diamine oxidase (DAO), reduced the pro-inflammatory cytokines (IL-1β, IL-6, IL-22) levels, while increasing the anti-inflammatory cytokine (IL-10) levels in serum of the colitis-obesity induced rat model. Moreover, the abundance of butyrate-producing bacteria, such as Oscillospiraceae and Butyricoccaceae, and Akkermansia, was enhanced after consuming whole wheat sourdough bread, in a strain-dependent manner. Importantly, a significantly higher content of short-chain fatty acids (SCFAs) was found in the feces for the two LAB-fermented sourdough groups, which counteracted the antinutritional factors in whole wheat. Furthermore, the transcriptomic and metabolomic analysis suggested that the underlying mechanism in the LF group was linked to the suppressed MAPK signaling pathway and activated T cell-mediated immune regulation, whereas in the LC group the mechanism involved enhanced DNA repair, activation of T/B-cell responses, and modulation of the vascular microenvironment through antioxidant pattern (ascorbic acid). Meanwhile, enhanced energy metabolism (α-ketoglutaric acid, carnitine) and anti-apoptotic effects (ceramide) were also achieved following this intervention. In conclusion, although LAB strain dependence was observed, the current findings revealed that intake of whole wheat sourdough bread ameliorated the symptoms of colitis in the colitis-obesity rat model via the regulation pattern of the "LAB fermentation → butyrate-producing bacteria" metabolic axis.