Intake of Lactobacillus reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans: A Proof of Concept

Abstract

OBJECTIVEIngestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents. We hypothesized that daily intake of Lactobacillus reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of the release of glucagon-like peptides (GLP)-1 and -2. RESEARCH DESIGN AND METHODSA prospective, double-blind, randomized trial was performed in 21 glucose-tolerant humans (11 lean: age 49 6 7 years, BMI 23.6 6 1.7 kg/m 2 ; 10 obese: age 51 6 7 years, BMI 35.5 6 4.9 kg/m 2 ). Participants ingested 10 10 b.i.d. L. reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemichyperinsulinemic clamps with [6, H 2 ]glucose were used to measure peripheral insulin sensitivity and endogenous glucose production. Muscle and hepatic lipid contents were assessed by 1 H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays. RESULTSIn glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2 release by 76% (P < 0.01) and 43% (P < 0.01), respectively, compared with placebo, along with 49% higher insulin (P < 0.05) and 55% higher C-peptide secretion (P < 0.05). However, the intervention did not alter peripheral and hepatic insulin sensitivity, body mass, ectopic fat content, or circulating cytokines. CONCLUSIONSEnrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic approach to improve glucose-dependent insulin release.Type 2 diabetes results from decreased insulin sensitivity and inadequate insulin secretion, which associate with diminished incretin response and subclinical chronic inflammation and subsequent impaired glucose tolerance (1-4). These pathogenic factors, frequently accompanied by hypercaloric high-fat low-fiber diets, may be associated with alterations in gut microbiota, which also occur in obesity (5) and type 2 diabetes (6).

Dysbiosis of urinary microbiota is positively correlated with Type 2 diabetes mellitus

“…Treatment with Lactobacillus can reduce the incidence of UTIs [32], and can reduce FBG, homocysteine, and interleukin-6 which play roles in preventing infection for diabetic patients [33–35]. In addition, the higher proportion of Lactobacillus can increase insulin secretion [36]. Therefore, increased Lactobacillus might be considered a protective effect on T2DM patients from infections and reducing blood glucose.…”

The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids

“…In line with these findings, Cani et al [93] found reduced hunger rates, increased postprandial GLP-1 and PYY, and decreased postprandial glucose responses in healthy volunteers treated with prebiotics. Probiotics, especially Lactobacillus strains, were also found to beneficially affect body weight, glucose-and lipid metabolism, and inflammatory status [94][95][96][97].…”

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease

“…In T2DM and NAFLD there is often a "functional" dysbiosis, with changes in microbial species affecting the metabolic and proinflammatory pathways (such as Akkermantia muciniphila and Faecalibacterium prausnitzii) that affect gut oxidative stress and butyrate production [68][69][70][71] . Increased amounts of Akkermantia muciniphila are also associated with higher L-cell activity (i.e., the neuroendocrine cells in the small intestine) with resulting increased glucagon-like peptide-1 (GLP-1) production that may improve glucose tolerance and increase satiety 72 . There is also now some data suggesting that dysbiosis occurs in CKD and the most often reported changes in gut microbiome in CKD which are related to lower levels of Bifidobacteriaceae and Lactobacillaceae and to higher levels of Enterobacteriaceae 66 .…”

“…Akkermantia muciniphila is also associated with higher L-cell activity and resulting increased production of glucagon-like peptide -1 (GLP-1) that improves glucose tolerance and increases satiety 72 .…”