Partially Hydrolyzed Guar Gum Combined with a Low-Fat Diet Ameliorates Type 2 Diabetes Mellitus via Modulating Gut Microbiota and Fecal Metabolites

<b>Background</b>: Low-fat diet (LFD) is widely applied in type 2 diabetes mellitus (T2DM), but the limited efficacy and difficulty in maintaining it hinder its wider promotion. Partially hydrolyzed guar gum (PHGG) is well-known as a probiotic in modulating gut microbiota, which is crucial in T2DM. However, the combined effects of LFD and PHGG remain unknown. <b>Methods</b>: Mice with T2DM were divided into 4 groups: T2DM control (DM-high-fat diet), LFD alone (DM-LFD), or LFD combined with low or high doses of PHGG (PHGG-L/H, 2.5% and 7.5% (<i>w</i>/<i>w</i>)) for 12 weeks. Serum lipid profiles, fasting blood glucose (FBG), HOMA-IR, and intraperitoneal glucose tolerance test (IPGTT) were assessed. Furthermore, microbiota composition, fecal metabolites, and fecal short-chain fatty acids (SCFAs) were determined by 16S rRNA gene sequencing, untargeted metabolomics, and gas chromatography-mass spectrometry, respectively. <b>Results</b>: LFD improved dyslipidemia but not glucose metabolism disorders. However, PHGG remarkably decreased FBG and HOMA-IR, and increased glucose tolerance. PHGG upregulated the abundance of SCFA-producing bacteria, including the genera <i>Dubosiella</i>, <i>Bifidobacterium</i>, and <i>Ruminococcus</i>, which were negatively correlated with FBG, HOMA-IR, and AUC (IPGTT). Moreover, the metabolic pathways altered by PHGG were enriched in tryptophan, tyrosine, and galactose metabolism. Fecal propionic acid and butyric acid, positively correlated with the abundance of genera <i>Dubosiella</i> and <i>Ruminococcus</i>, were markedly decreased by 50% and 44% in the DM-LFD group, but increased 2-fold after PHGG supplementation. <b>Conclusions</b>: PHGG combined with LFD might be a potential strategy to ameliorate glucose metabolic disorders, likely through modulating gut microbiota and the production of propionic acid and butyric acid.