Effect of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in subjects with metabolic syndrome: impact of low baseline gut Akkermansia levels.
The study found no significant improvement in overall insulin sensitivity with Akkermansia muciniphila, but some subgroups showed potential benefits in insulin sensitivity and GLP-1 levels.
Where it sits
this study against the rest of the liraglutide corpusSummary and findings
This study evaluated the effects of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in 142 adults with metabolic syndrome over a 4-month period. The primary endpoint of whole-body insulin sensitivity did not differ significantly between the treatment and placebo groups. However, exploratory analyses indicated some improvements in specific subgroups.
Abstract
Pasteurized Akkermansia muciniphila MucT was found to improve barrier function in preclinical models and a proof-of-concept study in obese and prediabetic adults. Here, we describe the results of a double-blind placebo-controlled multicenter (Ireland and Germany) trial in 142 adults with metabolic syndrome, with or without prediabetes. The primary endpoint of whole-body insulin sensitivity (Matsuda index) did not differ after 4-months of daily administration of capsules containing 30 billion cells of pasteurized A. muciniphila MucT compared to placebo in the intention-to-treat subjects. Subsequent exploratory analyses showed that 3-months intake of pasteurized A. muciniphila MucT already improved HOMA-based hepatic insulin sensitivity in prediabetic (12%; p = 0.05) and 63-y-or-older-age subgroups (p = 0.05) while increasing post-OGTT excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) over placebo (p < 0.01). Further analysis of the gut microbiota by deep metagenomic analysis showed minor effects of the intervention but revealed that the baseline microbial composition differed from that in matched healthy adults. We found that participants with low baseline Akkermansia gene counts experienced significant health improvements and GLP-1 excursion after 3-months of treatment with pasteurized A. muciniphila MucT over the placebo. These benefits included improved insulin sensitivity (as shown by Matsuda and HOMA-S indices) and GLP-1 excursion (post-OGTT) (p < 0.05), reductions in body weight (p = 0.06) and decreased trunk fat (p < 0.05). In conclusion, daily supplementation with pasteurized A. muciniphila MucT has the potential to improve health markers in overweight or obese normo- or dysglycemic adults with the most significant improvements in subjects with low baseline intestinal Akkermansia levels, who are apparently truly in need of this intervention. Clinical trial registration no.: NCT05114018 clinicaltrials.gov.
Background
The study investigates the role of pasteurized Akkermansia muciniphila in improving metabolic health, particularly insulin sensitivity, in adults with metabolic syndrome. Prior research indicated potential benefits of Akkermansia muciniphila on gut barrier function and metabolic markers, but this study aims to clarify its effects in a controlled setting. Understanding the impact of gut microbiota on metabolic health is crucial given the rising prevalence of metabolic syndrome.
Methods
This was a double-blind, placebo-controlled, multicenter trial conducted in Ireland and Germany involving 142 adults with metabolic syndrome. Participants received either 30 billion cells of pasteurized Akkermansia muciniphila MucT or placebo daily for 4 months. The primary outcome was whole-body insulin sensitivity measured by the Matsuda index, with secondary outcomes including HOMA-S indices and GLP-1 levels.
Results
The primary endpoint of whole-body insulin sensitivity did not show a significant difference after 4 months of treatment, with no specific numeric results provided. However, exploratory analyses revealed a 12% improvement in HOMA-based hepatic insulin sensitivity in the prediabetic subgroup (p=0.05) and significant increases in GLP-1 excursion post-OGTT (p<0.01). Body weight reduction was noted but did not reach statistical significance (p=0.06).
Interpretation
The findings suggest that while the primary endpoint did not demonstrate significant improvement, certain subgroups experienced notable benefits, particularly in hepatic insulin sensitivity and GLP-1 levels. However, the clinical significance of these findings is uncertain, especially given the exploratory nature of the analyses and the lack of robust primary endpoint results. The study may be limited by its reliance on subgroup analyses, which can introduce confounding factors.
Key findings
- No significant difference in whole-body insulin sensitivity (Matsuda index) after 4 months, n=142.
- 12% improvement in HOMA-based hepatic insulin sensitivity in prediabetic subgroup, p=0.05.
- GLP-1 excursion increased post-OGTT compared to placebo, p<0.01.
- Body weight reduction approached significance, p=0.06.
- Decreased trunk fat, p<0.05.
Limitations
- Primary endpoint showed no significant difference.
- Exploratory analyses may not be clinically meaningful.
- Reliance on subgroup analyses raises concerns about robustness.
- 4-month duration may be insufficient to assess long-term effects.
- No clear effect size reported for primary outcome.