New probiotic treatment for obesity and diabetes [PreClinical]

1. Administering various formulations of the Akkermansia (A.) muciniphila bacterium to mice resulted in improved metabolism and decreased weight gain.

2. A. muciniphila decreased body weight through various mechanisms and was found to be well tolerated in humans.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Although A. muciniphila is normally one of the most abundant bacteria strains in the intestine, levels of this strain are decreased in obese and diabetic patients. In contrast, increased levels have been found to improve cardiovascular health. Given this background, the goals of this study were to determine the specific mechanism of action of this bacterium as well as to improve its therapeutic applicability.

Mice were placed on a high fat diet and then administered either pasteurized or unpasteurized forms of the bacterium. Both groups were found to have a significant decrease in fat mass gain compared to animals without treatment. The treated mice were also found to have a higher glucose tolerance, lower insulin resistance, and lower energy absorption. In addition, this bacterium decreased the expression of a gene known to be involved in the development of atherosclerosis and insulin resistance. The researchers found that A. muciniphila exerted its effects through the TLR2 receptor, leading to improved gut barrier function through the regulation of tight-junction proteins.

Clinical studies have begun to test the safety and efficacy of probiotics containing this bacterium in obese patients. So far, the formulations have been found to be safe to administer with few to no side effects. As more subjects are being recruited for the study, the efficacy of this bacterium on weight loss and overall health will be assessed.

Click to read the study in Nature Medicine

Relevant Reading: Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

In-Depth [animal and human study]: First, mice were fed a high fat diet and administered A. muciniphila grown on a mucus-based medium, a synthetic medium more compatible for human administration, or pasteurized for 30 minutes at 72^oC. The mice given the pasteurized bacteria had the largest decrease in body weight gain (p<0.001). Due to the greater efficacy of the pasteurized bacteria, this formulation was used in subsequent experiments. The mice given pasteurized bacteria demonstrated lower insulin resistance and decreased plasma glucose levels (p<0.01). In addition, they excreted more calories in their feces (p< 0.05), indicating lower energy absorption. Mice treated with the pasteurized bacteria did not show the increase in Fmo3 expression induced by a high fat diet (p<0.05), potentially leading to the protection of these mice against atherosclerosis and insulin resistance.

The researchers then wanted to determine the mechanism of action through which this bacterium exerted its effects in the intestine. Through genomic and proteomic analyses, Amuc_100 was found to be the most abundant outer membrane protein in A. muciniphila. This protein was then introduced to E. coli and was found to signal through the TLR2 receptor. In mice, administration of Amuc_100 led to the correction of high fat diet-induced hypercholesterolemia (p< 0.05), as well as the increased expression of genes encoding tight-junction proteins that maintain gut barrier function.

Currently, clinical trials of probiotics containing A. muciniphila are underway to evaluate their therapeutic safety and efficacy in obese individuals. Preliminary data included in this study showed that when individuals were treated with different doses of either live or pasteurized bacteria, both groups tolerated the treatment well.

Image: PD

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