Carob fruit extract-enriched meat, as preventive and curative treatments, improves gut microbiota and colonic barrier integrity in a late-stage T2DM model

Abstract

Epidemiological and experimental studies have suggested that dietary fiber and proanthocyanidins play an important role on gut microbiota (GM), colonic integrity and body health. Type 2 Diabetes Mellitus (T2DM) is a prevalent disease in which the modifications in the GM and colonic markers stand out. This manuscript hypothesizes the consumption of functional meat enriched in carob fruit extract [CFE; CFE-restructured meat (RM)] ameliorates the dysbiosis and colonic barrier integrity loss in a late-stage T2DM rat model induced by the conjoint action of a high-saturated-fat/high-cholesterol diet (Chol-diet) and a low dose of streptozotocin (STZ) plus a nicotinamide (NAD) injection. Three groups of eight rats were used: (1) D group, a T2DM control group, fed the Chol-diet; (2) ED group, a T2DM preventive strategy group fed the CFE-Chol-diet since the beginning of the study; and (3) DE group, a T2DM curative treatment group, fed the CFE-Chol-diet once the diabetic state was confirmed. The study lasted 8 weeks. Amount and variety of GM, feces short-chain-fatty acids (SCFAs), colonic morphology [crypt depth and density, goblet cells, proliferating cell nuclear antigen (PCNA) and transferase dUTP nick end labelling (TUNEL) indexes] and tight junctions were evaluated. A global colonic index combining 17 markers (GC_index) was calculated. ED rats displayed higher levels of GM richness, SCFAs production, crypt depth, and goblet cells than the D group. DE group showed lower Enterobacteriaceae abundance and greater TUNEL index and occludin expression in the distal colon than D counterpart. GC_index differentiated the colonic health status of the experimental groups in the order (ED > DE > D; P < 0.001) as a 17-51 range-quotation, ED, DE, and D groups displayed the values 43, 32.5, and 27, respectively. Thus, CFE-RM used as a T2DM preventive therapy could induce higher GM richness, more adequate SCFAs production, and better colonic barrier integrity. Furthermore, CFE-RM used with curative purposes induced more modest changes and mainly at the distal colonic mucosa. Further studies are needed to confirm this study's results, to ascertain the benefits of consuming proanthocyanidins-rich fiber during different T2DM stages.

Keywords: Carob fruit extract-enriched meat; Colonic barrier integrity; Colonic indexes; Functional food; Gut microbiota; SCFAs; late stage T2DM.