Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: A proof-of-concept exploratory study
Open accessAbstract
Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus 1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders 2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension 3-8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 10 10 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115 ) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.
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In mice, administration of A. muciniphila prevents the development of obesity and associated complications.
“In mice, it has been shown that administration of A. Muciniphila prevents the development of obesity and associated complications.”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [314]
In humans, studies have provided evidence for a negative correlation between A. muciniphila abundance and overweight, obesity, untreated T2D, or hypertension.
“In humans, studies have provided evidence for a negative correlation between A. Muciniphila abundance and overweight, obesity, untreated T2D or hypertension.”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [314]
High relative proportions or subdominance of A. muciniphila in the ecosystem have been associated with pathophysiological failures.
“High relative proportions or subdominance of A. muciniphila in the ecosystem has been associated with pathophysiological failures (such as anorexia nervosa 48 , GVHD 33 , Aging 49 , dysmetabolism 50 , HIV infection 51 , pathobionts 52 or liver injury 53 ).”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [48]
A. muciniphila influences host metabolism to maintain glucose tolerance and intestinal barrier function.
“Akkermansia muciniphila is a Gram-negative homeostatic commensal bacteria that influences host metabolism to maintain glucose tolerance and intestinal barrier function.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [101]
Supplementation with pasteurised A. muciniphila improves metabolic dysfunctions and intestinal barrier integrity and reduces plasma lipopolysaccharide levels in obese human volunteers.
“Supplementation with pasteurised A. muciniphila improved metabolic dysfunctions and the integrity of intestinal barrier and reduced plasma lipopolysaccharide levels in obese human volunteers.16”
Recent studies showed that both pasteurised A. muciniphila and Amuc_1100 (stable after pasteurisation) could partly recapitulate the beneficial effects of the live bacterium.
“Recent studies showed that both pasteurised A. muciniphila and Amuc_1100 (stable after pasteurisation) could partly recapitulate the beneficial effects of the live bacterium.16 21”
Giving Akkermansia species by mouth improves body composition in obese patients.
“improves body composition in obese patients 61,62 .”
From Impact of the ONCOBIOME network in cancer microbiome research (2025) · cites this paper as [61]
Delayed age-associated microbiota changes in mice have been observed by BCAA consumption, displaying a greater abundance of Bifidobacterium and Akkermansia, which improve glucose homeostasis and insulin sensitivity.
“Furthermore, delayed age-associated microbiota changes in mice have been observed by BCAA consumption, displaying a greater abundance of Bifidobacterium and Akkermansia [210], which improve glucose homeostasis and insulin sensitivity [182,211,212].”
From Impact of Protein Intake in Older Adults with Sarcopenia and Obesity: A Gut Microbiota Perspective (2020) · cites this paper as [210]
Administration of pasteurized, but not live, Akkermansia muciniphila for 3 months led to reduction in plasma lipopolysaccharide in obese individuals with metabolic syndrome.
“a recent proof-of-concept study in humans found that administration of pasteurized (but not live) Akkermansia muciniphila for 3 months led to reduction in plasma LPS in obese individuals with metabolic syndrome29.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [29]
The Akkermansia intervention did not change body weight but improved insulin sensitivity and dyslipidemia in the treated group.
“Although the intervention did not change body weight, the authors observed improvement in insulin sensitivity and dyslipidemia in the Akkermansia-treated group.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [29]
In a randomized placebo-controlled double-blinded interventional exploratory study, provision of Akkermansia muciniphila promoted a reduction in plasma LPS in obese individuals with metabolic syndrome.
“For example, provision of Akkermansia muciniphila in a randomized placebo controlled double blinded interventional exploratory study was reported to promote a reduction in plasma LPS in obese individuals with metabolic syndrome29.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [29]
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- Authors
- Depommier, C., Everard, A., Druart, C., Plovier, H., Van Hul, M., Vieira-Silva, S., Falony, G., Raes, J., Maiter, D., Delzenne, N. M., de Barsy, M., Loumaye, A., Hermans, M. P., Thissen, J.-P., de Vos, W. M., & Cani, P. D.
- Affiliations
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- VIB-KU Leuven Center for Microbiology (BE)
- Cliniques Universitaires Saint-Luc (BE)
- UCLouvain (BE)
- Corresponding author
- Cani, Patrice D.
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-07
- Volume
- 25
- Issue
- 7
- Pages
- 1096-1103
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6699990
- OpenAlex
- W2954124338
- Cited by
- 2,357
- References
- 51
- Citations by year
- 2026: 341 · 2025: 353 · 2024: 347 · 2023: 322 · 2022: 378 · 2021: 318 · 2020: 246 · 2019: 46 · 2018: 1 · 2012: 1
- FWCI
- 82.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Lirias (KU Leuven) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- Akkermansia muciniphila, probiotic supplementation, obesity, overweight, insulin resistance, metabolic syndrome, gut microbiota, lipopolysaccharide, visceral fat, weight loss, total cholesterol, insulin levels, liver function markers, inflammation, safety and tolerability, type 2 diabetes, hypertension, intestinal barrier
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Double-Blind Method, Feces, Humans, Insulin Resistance, Middle Aged, Obesity, Pilot Projects, Dietary Supplements, Overweight, Verrucomicrobia
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