A Novel Antidiabetic Monomers Combination Alleviates Insulin Resistance Through Bacteria-Cometabolism-Inflammation Responses

Abstract

The present study sought to examine the therapeutic effect of a novel antidiabetic monomer combination (AMC) in treating type 2 diabetes mellitus (T2DM); while also elucidating the potential functional mechanism. Male C57BL/6J mice were fed a highfat diet (HFD) for 12 weeks to establish T2DM. The AMC group showed significant reduction in weight, fasting blood glucose (FBG), serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), and experienced reduced insulin resistance based on oral glucose tolerance testing (OGTT) and hyperinsulinemic-euglycemic clamp testing ("gold standard" for determining in vivo insulin sensitivity). Further, AMC restored the altered intestinal flora by increasing the abundance of the beneficial bacteria Akkermansia, and decreasing the number of harmful bacteria, including Bacteroides, Odoribacter, Prevotella 9, Alistipes, and Parabacteroides. Components of the hostmicrobial metabolome were also significantly changed in the AMC group compared to the HFD group, including hydroxyphenyllactic acid, palmitoleic acid, dodecanoic acid, linoleic acid, and erucic acid. Furthermore, AMC was found to inhibit inflammation and suppress signaling pathways related to insulin resistance. Lastly, spearman correlation analysis revealed relationships between altered microbial community and co-metabolite levels, co-metabolites and inflammatory cytokines. Hence, the potential mechanism responsible for AMC-mediated alleviation of insulin resistance was suggested to be involved in modulation of bacteria-cometabolism-inflammation responses.

Dietary supplementation with Bacillus subtilis promotes growth performance of broilers by altering the dominant microbial community

“…Based on Kyoto Encyclopedia of Genes and Genome prediction, the abundant functional annotations of cecal microbiota were those corresponding to carbohydrate metabolism, amino acid metabolism, membrane transport, replication and repair, energy metabolism, translation, poorly characterized, nucleotide metabolism, cellular processes and signaling, and metabolism of cofactors and vitamins. These predicted functions of cecal microbiota in broilers were similar to those predicted by other studies ( Ma et al., 2018 ; Hu et al., 2020 ). However, the addition of B. subtilis or zinc bacitracin had little effect on the predicted functions of cecal microflora in broilers.…”

“… Salaheen et al. (2017) and Hu et al. (2020) also reported that supplementing broilers with antibiotic growth promoters (tylosin, neomycin sulfate, bacitracin, erythromycin, and oxytetracycline or virginiamycin) increased the abundance of Proteobacteria .…”

“… Liu et al. (2019) reported that proteoglycan induced mice with Ankylosing spondylitis exhibited notably increased relative abundances of Odoribacter , and Han et al. (2020) also thought Odoribacter was positively correlated with the inflammatory state.…”

Alteration of Intestinal Microbiota in 3-Deoxyglucosone-Induced Prediabetic Rats

“…The bacteria of the Parasutterella genus were shown to positively correlate with the chronic inflammatory state and drove insulin resistance [ 27 ]. The abundance of Parasutterella remarkably increased in HFD-induced T2D mice and decreased after the treatment of novel antidiabetic monomers [ 28 ]. The Candidatus Soleaferrea genus was known to possess anti-inflammatory effects by secreting metabolites and intestinal homeostasis protection properties [ 29 , 30 ].…”

The Interaction between Mitochondrial Oxidative Stress and Gut Microbiota in the Cardiometabolic Consequences in Diet-Induced Obese Rats

“…Our data show that 5 genera were independent predictors of HOMA (an index of insulin resistance), 2 of them in a positive manner ( Candidatus soleaferrea and Peptoclostridium ) and 3 in a negative one ( uncultured Muribaculaceae, Eubacterium oxidoreducens group and Holdemania ). Different data have also reported the association between insulin resistance and the levels of these genera [ 14 , 34 , 35 , 36 ].…”