Daily supplementation with an Akkermansia muciniphila probiotic led to marked improvement in fasting blood glucose, post-prandial glucose, and hemoglobin A1c after 60 days.
Those are the upshots of a new placebo-controlled study involving 60 prediabetic individuals. The findings strengthen the case for clinical use of Akkermansia in the management of people at high risk for type 2 diabetes (T2D).
“Akkermansia muciniphila ameliorates T2D hallmarks like insulin resistance and metabolic syndrome by enhancing glucose, lipid, and bile acid metabolism. Its metabolite propionate, stimulates GLP-1 secretion to boost insulin release and suppress appetite, while P9 protein with ICAM-2 activates GLP-1 pathways,” report Prabhu Rajagopalan and colleagues who undertook the study.
The beneficial biomarker changes seen among the probiotic-treated subjects were accompanied by significant reductions in body weight, body mass index (BMI), and waist circumference. The treated patients also showed a statistically significant reduction in diastolic blood pressure compared with the placebo group, though there were no changes in systolic pressure, total cholesterol, LDL, or HDL.
Mounting Evidence
The new trial builds on prior evidence suggesting that A. muciniphila can influence human metabolism in ways that potentially reduce diabetes risk.
Population studies have shown that levels of A. muciniphila–a mucin-degrading bacterium comprising up to 3-5% of the healthy gut microbiota—correlate inversely with obesity, prediabetes, and dyslipidemia. Animal studies indicate that A. muciniphila supplementation can improve insulin sensitivity, glucose tolerance, and lipid profiles in rodents fed a high-fat diet.
A previous proof-of-concept human study showed that compared with placebo, Akkermansia taken daily over 3 months improved insulin sensitivity by 28.6%, lowered insulinemia by 34.1%, and reduced total cholesterol by 8.7% in a cohort of overweight/obese people. In that study there was also a slight but non-significant decrease in body weight and fat mass.
The current study was done by researchers at an Indian natural products company called Vidya, to test the efficacy of their new Akkermansia-based probiotic called NuGensia.
Pre-Diabetic Cohort
They initially recruited 143 men and women between the ages of 31-60, diagnosed as prediabetic according to current American Diabetes Association criteria (A1c of 5.7–6.4%; Fasting blood glucose 100–125 mg/dL) and OGTT two-hour blood glucose of 140–199 mg/dL). Of that original cohort, 83 were excluded due to concurrent hypertension, gastrointestinal disease, liver or kidney problems, or immunocompromising conditions.
The 60 participants were randomized to daily oral supplementation with a probiotic containing Vidya’s patented strain of live A. muciniphila (10B CFU per day) or a maltodextrin placebo. The treatment period was for 60 days, after which the participants underwent full biomarker and biometric assessment.
At baseline, the placebo and probiotic groups were generally comparable on all key measures of glucose and lipid metabolism. By Day 60, there were a number of important and statistically significant changes.
Meaningful Weight Loss
The probiotic group showed significantly lower fasting glucose levels (109.4 ± 14.6 vs 113.0 ± 14.9 mg/dL; p = 0.0338), as well as lower post-prandial glucose (131.7 ± 25.5 vs 145.7 ± 25.4 mg/dL; p = 0.0373). Notably the mean HbA1c was roughly 14% lower among those taking the probiotic (4.78 ± 0.17 vs 5.55 ± 0.64%; p = 0.0428).
Triglyceride (TGL) levels did not change among the placebo-treated patients, but they did drop considerably in the probiotic group. On Day 60, the mean TGL was 122.4 ± 42.4 mg/dL following probiotic treatment, versus 151.1 ± 54.9 mg/dL in the placebo group. That’s a 19% drop.
That said, there were no other significant changes in lipid markers.
Akkermansia supplementation was associated with significant weight loss. The patients taking the probiotic lost an average of 4.4 Kg over the 60-day period, going from 68.55 Kg at baseline, to 64.15 Kg at the close of the study. That’s a 6.4% drop, just from the probiotic without any dietary or exercise interventions.
Not surprisingly, this correlated with a statistically significant drop in body-mass index and a reduction in mean waist circumference.
In contrast, there was a slight 0.69 mean weight gain among the placebo patients over the 60-day treatment period, with no meaningful change in BMI or waist circumference.
There were no adverse effects reported by the 30 participants who took the probiotic. This echoes the conclusion of a metanalysis of prior Akkermansia studies indicating only mild GI effects at an incidence rate of under 5%.
A “Therapeutic Microbe”
“Through our study we have demonstrated that oral supplementation with Akkermansia muciniphila significantly improved glycemic control, triglyceride levels, central adiposity, and diastolic blood pressure in prediabetic adults over 60 days, with an exemplary safety profile,” write Dr. Rajagopalan and colleagues.
They attributed the diastolic pressure decrease “to reduced visceral adiposity and inflammation, mechanisms validated in microbiota-obesity studies.”
Akkermansia muciniphila produces a number of metabolites that enhance human glucose, lipid, and bile acid metabolism. Propionate, a key compound produced by this organism, stimulates GLP-1 secretion which triggers insulin release and suppress appetite.
Rajagopalan notes that A. muciniphila also activates hepatic PI3K-Akt signaling which improves glucose and lipid regulation, and influences a number of genes in intestinal cells. It reduces white adipose tissue, increases triglyceride clearance, and favorably alters bile acid metabolism.
With of its multi-pathway effects, the authors believe A. muciniphila should be considered “a therapeutic gut microbe,” and that it deserves a place as an adjunctive strategy for improving cardiometabolic health.
As with any company-funded and company-conducted clinical study, there’s potential for bias in favor of the company’s products, and we must keep this in mind in considering the study’s conclusions. Further, the study had a fairly small number of patients, at least by pharmaceutical standards, as well as a fairly short treatment period—limitations the authors clearly acknowledge.
That said, this new study does make a strong case for inclusion of the Vidya A. muciniphila probiotic in the care of people with metabolic dysregulation who are at high risk for type 2 diabetes.
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