Akkermansia muciniphila

Akkermansia muciniphila

1. Identity and Classification

Taxonomic Identity

Akkermansia muciniphila is a mucin-degrading bacterium belonging to the genus Akkermansia, discovered in 2004 by Muriel Derrien and Willem de Vos at Wageningen University of the Netherlands. It belongs to the phylum Verrucomicrobiota, and its type strain is MucT (=ATCC BAA-835^T =CIP 107961^T).

Akkermansia muciniphila is a Gram-negative, strictly anaerobic, non-motile, non-spore-forming bacterium, and is culturable under anaerobic conditions on medium containing porcine gastric mucin or synthetic medium containing a protein source with glucose, N-acetylglucosamine, and N-acetylgalactosamine.

The organism was first identified in 2002 as a mucin-related bacterium, oval-shaped, with 0.6–1.0 µm cell size. The circular chromosome of the type strain contains 2,664,102 base pairs, and its proteome contains 5,644 unique proteins.

The genus name honors microbial ecologist Antoon D.L. Akkermans, while the species epithet muciniphila translates as "preferring mucin." As its species name implies, this verrucomicrobial bacterium degrades mucin, an important component of the mucus layer lining the intestinal epithelium.

The mucophilic anaerobic bacterium Akkermansia muciniphila is a prominent member of the gastrointestinal (GI) microbiota and the only known species of the Verrucomicrobia phylum in the mammalian gut.

Natural Occurrence

A. muciniphila is a common resident of the human gut, representing approximately 1%–3% of the total gut microbiota. This bacterium accounts for about 1–4% of the total fecal microbiota population and is also considered a health marker.

A. muciniphila resides in the mucus layer of the large intestine, where it is involved in maintaining intestinal integrity. Signatures of A. muciniphila were detected in colonic samples as early as a few weeks after birth and are likely maintained throughout life.

Akkermansia species occur in many different animal species, from pythons to horses, as well as humans and model laboratory rodents. The genus Akkermansia has also been found in human breast milk, which may be due to the organism's ability to use human milk oligosaccharides.

Lipopolysaccharide Structure

The lipopolysaccharide (LPS) of A. muciniphila has been found to lack the O-antigen unit, making it a lipooligosaccharide (LOS), also known as rough-type LPS. The LOS has been found to consist of two core oligosaccharides: an undeca- and a hexadecasaccharide chain. A. muciniphila LOS has been found to induce moderately strong TLR4 activation in vitro, and the lipid A moiety has been shown to strongly induce TLR2 activation, likely through the TLR2/6 heterodimer.

Supplemental Forms and Preparations

Akkermansia muciniphila is not a botanical herb or a conventional dietary ingredient but rather a live microorganism (or preparation derived from it), commonly described as a "next-generation probiotic" or "postbiotic." It is commercially available in two primary forms:

• Live (viable) form: Intact, metabolically active bacteria, requiring strict anaerobic cultivation and cold-chain storage.
• Pasteurized (heat-treated) form: The heat stability of surface proteins explains why A. muciniphila retains most of its effects even after pasteurization. In the European Union, the company A-Mansia Biotech S.A. submitted a request in October 2019 to place pasteurized Akkermansia muciniphila on the market as a novel food. Pasteurized Akkermansia muciniphila is intended to be used in food supplements and in foods for special medical purposes.
• Isolated outer membrane proteins (e.g., Amuc_1100): Purified protein fractions derived from the outer membrane, under investigation as active ingredients independent of intact bacteria.
• Extracellular vesicles (AmEVs): Nanovesicles produced and shed by the organism, investigated in preclinical models for several of the same effects ascribed to intact cells.

2. Historical and Traditional Use

Akkermansia muciniphila has no documented history of traditional use as a medicinal ingredient. As a defined bacterial species, it did not exist as a recognized entity in any pre-modern pharmacopeial, ethnobotanical, or traditional medicine tradition. It was discovered in 2004 by Muriel Derrien and Willem de Vos at Wageningen University.

In 2004, Muriel Derrien, in her Ph.D. research at Wageningen University of the Netherlands, isolated from a sample of healthy human feces a species of bacteria that can grow on a viscogenic substrate such as mucin and use it as a single nutrient source, especially on the mucosal surface of the gastrointestinal tract.

Described in 2004 by Derrien et al., this bacterium is able to use mucin as its sole carbon source; it participates in the renewal of mucus and the integrity of the intestinal barrier. Ever since Akkermansia muciniphila was discovered and characterized two decades ago, numerous studies have shown that the lack or decreased abundance of this commensal bacterium was linked with multiple diseases (such as obesity, diabetes, liver steatosis, inflammation, and response to cancer immunotherapies).

Accordingly, the entire scientific and clinical record for A. muciniphila is contemporary, with no traditional-use data to separate from modern evidence. Research activity has grown rapidly, particularly after 2013, advancing from observational and animal studies to, more recently, human proof-of-concept trials.

3. Key Constituents and Active Compounds

Mucin Utilization and Short-Chain Fatty Acid Production

Mucins are produced by goblet cells of the intestinal epithelium. They are highly glycosylated molecules containing serine, threonine, and cysteine amino acids, and they form a transparent mucus layer on the intestinal tissue surface. The type strain MucT was isolated as a species capable of degrading mucin glycoprotein, using it as a source of both carbon and nitrogen.

A. muciniphila can produce acetate, succinate, and propionate as short-chain fatty acids (SCFAs). Akkermansia generates SCFAs from the breakdown of mucins, which stimulates goblet cells to produce more mucus, thereby preserving and replenishing the intestinal barrier integrity.

Outer Membrane Protein Amuc_1100

The gut microbiota-derived protein Amuc_1100, a key outer membrane component of Akkermansia muciniphila, has emerged as a groundbreaking therapeutic agent with unique structural and functional properties. Amuc_1100, which is a 32 kDa pili-like protein composed of four α-helixes and a four-strand antiparallel β-fold, is one of the most expressed outer membrane proteins of A. muciniphila.

The purified Amuc_1100 protein and enrichments containing its associated proteins induced production of specific cytokines through activation of Toll-like receptor (TLR) 2 and TLR4, leading mainly to high levels of interleukin-10 (IL-10), similar to those induced by other beneficial immunosuppressive microorganisms such as Faecalibacterium prausnitzii and Lactobacillus plantarum.

Amuc_1100 remains stable under various temperatures and pasteurization treatments, and can regulate host immune homeostasis and gut barrier function in the intestinal mucosa through mechanisms such as modulation of TLR2/4 and JAK/STAT pathways, while bypassing risks associated with live bacterial administration.

Amuc_1100 has been identified as an outer membrane protein that activates intracellular signals mediated by TLR2 of intestinal epithelial cells, contributing to enhancement of the intestinal barrier. It is also involved in the immune response, specifically in the induction of IL-10, which is an anti-inflammatory cytokine.

Extracellular Vesicles (AmEVs)

AmEVs, serving as nanovesicles carrying bioactive molecules, increase tight junction protein expression via an AMPK-dependent pathway in Caco-2 cell models and high-fat-diet-induced diabetic mice, significantly improving intestinal barrier integrity. The organism's extracellular vesicles are believed to be a secondary mechanism through which A. muciniphila communicates its effects to host cells at a distance.

SCFA-Mediated AMPK and Endocannabinoid Signaling

A. muciniphila can modulate two significant regulators in lipid and glucose metabolism: adenosine 5′-monophosphate-activated protein kinase (AMPK) and the endocannabinoid system (ECS). Mucin degradation potentially releases fatty acids, such as arachidonic acid, which serve as essential precursors for the synthesis of endocannabinoids like AEA and 2-AG. A. muciniphila supplementation has been shown to significantly elevate circulating and intestinal levels of AEA, 2-AG, and 2-PG, consistent with this metabolic pathway. Furthermore, SCFAs, key metabolites of A. muciniphila, may also modulate ECS activity via G protein-coupled receptor signaling.

Tryptophan and Bile Acid Metabolism

The presence of Akkermansia muciniphila influences tryptophan derivatives, including indoleamine 2,3-dioxygenase 1 (IDO1) products, affecting gut-brain signaling and neuroprotection. A. muciniphila's impact also extends to the host's bile acid pool, where it can modify bile acid profiles, influencing host lipid and glucose metabolism.

Additionally, Akkermansia muciniphila's influence on the production of gamma-aminobutyric acid (GABA), a neurotransmitter crucial for brain function, highlights its role in the gut-brain axis.

4. Mechanisms of Action

Gut Barrier Reinforcement

A. muciniphila enhances the gut barrier to defend against intrusion of harmful particles and pathogens in several ways. Firstly, A. muciniphila upregulates expression of tight-junction proteins including claudin-1 and zonula occludens (ZO)-1.

Increased colonization of A. muciniphila in the colon of mice upregulated and activated intestinal CREBH, which subsequently mitigated intestinal endoplasmic reticulum (ER) stress, gut barrier leakage, and blood endotoxemia. The mechanistic study revealed that CREBH positively regulated the expression of tight junctions that contribute to gut barrier integrity (e.g., CLDN5 and CLDN8) but inhibited the leaky gut tight junction CLDN2, leading to inhibition of gut permeability and inflammation.

Upregulation of CREBH by A. muciniphila, further coupled with miR-143/145, promoted intestinal epithelial cell (IEC) regeneration and wound repair via insulin-like growth factor (IGF) and IGFBP5 signaling.

Immune Modulation

Amuc_1100 exerts multifaceted immune-metabolic effects through novel mechanisms, including modulation of TLR2/4 and JAK/STAT pathways. This enables synergistic biological activity and its pharmacological properties underlie its ability to enhance intestinal barrier integrity, restore microbiota balance, and suppress systemic inflammation.

A. muciniphila can activate colonic RORγt Treg-mediated immune responses via TLR4, thus mitigating colitis to maintain intestinal homeostasis.

A. muciniphila also maintains microbial balance by competing with and inhibiting the overgrowth of other mucin-degrading bacteria.

Mucus Layer Dynamics

As the species name implies, this verrucomicrobial bacterium degrades mucin, an important component of the mucus layer lining the intestinal epithelium. Mucins are produced by goblet cells of the intestinal epithelium and are highly glycosylated molecules that form a transparent mucus layer on the intestinal tissue surface. Paradoxically, by consuming mucins, A. muciniphila stimulates renewed production of mucin by goblet cells, resulting in a net thickening and renewal of the protective mucus layer rather than its depletion.

5. Scientific Evidence by Area of Use

5.1 Obesity and Metabolic Syndrome

Epidemiological and Correlative Evidence

In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus (T2DM), or hypertension. Consistent findings from both preclinical and clinical research have revealed declined abundance of A. muciniphila in obesity and metabolic syndromes.

Key Human Clinical Trial (Depommier et al., 2019)

A randomized, double-blind, placebo-controlled pilot study was conducted in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary endpoints were safety, tolerability, and metabolic parameters (insulin resistance, circulating lipids, visceral adiposity, and body mass).

Participants received either a placebo, live Akkermansia, or pasteurized Akkermansia daily for three months at a dose of 10 billion CFUs.

Key results from this trial (NCT02637115) published in Nature Medicine:

• 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.

This study provides a promising signal for the development of future clinical interventions with appropriate design to confirm and extend findings showing the safety and impact of oral supplementation with A. muciniphila in overweight or obese insulin-resistant individuals.

Evidence Strength Assessment

Although primarily based on simple associations, there are now an increasing number of studies moving from correlations to causality. The causal evidence derived from a variety of animal models has been performed in different laboratories and recently was also recapitulated in a human proof-of-concept trial. Nonetheless, the pivotal human trial enrolled only 32 completers and is explicitly described as a pilot proof-of-concept study. Evidence must currently be regarded as promising but preliminary, pending larger, adequately powered randomized controlled trials.

5.2 Type 2 Diabetes and Insulin Resistance

A number of studies have depicted the decrease or depletion of A. muciniphila in metabolic diseases including obesity and type 2 diabetes. The 2019 human trial described above demonstrated significant improvements in insulin sensitivity and insulinemia with pasteurized supplementation compared to placebo, providing the most direct human evidence to date.

As of the state-of-the-art review in 2022, there are three validly published studies that reported the safety of use and the beneficial role of A. muciniphila in obese humans as a probiotic, while two clinical trials were in progress to evaluate the effects of the use of A. muciniphila in obese patients with type 2 diabetes and in hyperglycemic adults (NCT04797442/NCT05114018). These trials remained ongoing at the time of that report. Evidence from type 2 diabetes–specific interventional studies in humans remains limited; existing human data on glycemic parameters derive primarily from the 2019 pilot trial in the insulin-resistant overweight population described above.

5.3 Gut Barrier Function and Intestinal Integrity

Mechanistic evidence — primarily from cell culture and animal studies — robustly supports a role for A. muciniphila in maintaining and restoring the intestinal epithelial barrier. Outer membrane protein composition, and particularly the highly abundant pili-like protein Amuc_1100 of A. muciniphila, is involved in host immunological homeostasis at the gut mucosa and improvement of gut barrier function.

Expression of Amuc_1100 in intestinal epithelial cells could recapitulate the health-beneficial effect of A. muciniphila on the gut by activating CREBH, inhibiting ER stress, and enhancing the expression of genes involved in gut barrier integrity and IEC regeneration. These findings are largely preclinical; direct measurements of gut permeability improvement in rigorous human interventional trials are limited.

5.4 Inflammatory Bowel Disease (IBD)

A number of studies have depicted the decrease or depletion of A. muciniphila in inflammatory bowel diseases, such as Crohn's disease, colorectal cancer, and ulcerative colitis. Akkermansia muciniphila is a key player in the colonic microbiota that resides in the mucus layer, and its abundance is selectively decreased in the fecal microbiota of IBD patients.

However, some studies have contradicted the role of A. muciniphila in colitis and inflammatory bowel disease (IBD), which may be attributed to strain differences. Some studies have contradicted the role of A. muciniphila in colitis and IBD, which may be attributed to strain differences. The evidence in this area is mixed, and clinical intervention data in human IBD patients are absent from the published literature at this time.

5.5 Cancer and Immunotherapy Response

An increasing body of research indicates that intestinal flora, particularly Akkermansia muciniphila, is vital for the treatment of tumors. Enrichment of A. muciniphila has been observed in patients who responded to immune checkpoint inhibitors, and administration of A. muciniphila could improve the antitumor efficacy of PD-1 blockade.

Pasteurized A. muciniphila or Amuc_1100 was reported to reduce colitis symptoms and tumor growth by increasing CD8+ T cell recruitment and elevating TNFα expression while lowering the checkpoint programmed cell death 1 (PD-1) in animal studies.

In mouse cancer models under anti-PD-1 immunotherapy combined with oral administration of three forms of Akk (live Akk, pasteurized Akk, or Amuc_1100), live Akk was most effective in activation of CD8 T cells by rescuing the exhausted type into cytotoxic subpopulations.

Evidence for the cancer-immunotherapy association in humans is primarily observational and correlative. No prospective interventional trial has yet established that deliberate supplementation with A. muciniphila improves clinical outcomes in cancer patients receiving immunotherapy.

5.6 Cardiovascular Disease

A. muciniphila has been shown to significantly attenuate high-fat-diet-induced atherosclerosis in preclinical models, a process characterized by a profound modulation of the host endocannabinoid system (ECS). Specific molecules and mechanisms of A. muciniphila and its derivatives have been detailed in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease in animal and observational human studies. Human interventional evidence specific to cardiovascular endpoints remains preclinical or correlative.

5.7 Non-Alcoholic Fatty Liver Disease (NAFLD)

A. muciniphila has been implicated in the progression of various diseases, including non-alcoholic fatty liver disease (NAFLD). The 2019 human trial reported that, after three months of supplementation, liver dysfunction blood markers were reduced compared to placebo. However, NAFLD-specific interventional human trials have not yet been published.

5.8 Neurological and Gut-Brain Axis Effects

In the context of neurological diseases, A. muciniphila significantly influences the host brain through the microbiota–gut–brain axis (MGBA). Relevant active components include the outer membrane protein Amuc_1100, extracellular vesicles (AmEVs), and SCFAs; and the spectrum of neurological disorders under investigation includes Alzheimer's disease (AD), Parkinson's disease (PD), depression, cerebral palsy (CP), epilepsy (EP), autism spectrum disorder (ASD), and amyotrophic lateral sclerosis (ALS).

Proposed protective effects include enhancing the intestinal barrier, regulating lipid metabolism, producing SCFAs, secreting neuroactive substances, and inhibiting neuroinflammation.

However, due to limited data from large-scale human clinical trials and the complexity of disease mechanisms and host–microbiota interactions, its clinical translation faces considerable challenges. Future efforts should focus on multicenter randomized controlled trials and in-depth mechanistic studies utilizing technologies such as metabolomics to facilitate evidence-based clinical application.

Evidence in this area is currently limited to preclinical models and cross-sectional observational human studies. No interventional human trials specifically targeting neurological outcomes have been published.

6. Body Systems Associated

• Gastrointestinal / Gut Barrier: A. muciniphila resides in the mucus layer of the large intestine, where it is involved in maintaining intestinal integrity.
• Metabolic / Endocrine: The accumulated evidence has shown a significant association between A. muciniphila and several disorders and diseases, such as obesity, fatty liver disease, and diabetes.
• Immune: The considerable role of A. muciniphila as a member of the gut microbiome in immune function and the intestinal ecosystem is well documented.
• Cardiovascular: Preclinical evidence supports a role in attenuating diet-induced atherosclerosis through endocannabinoid and lipid metabolism modulation.
• Hepatic: Reductions in liver dysfunction biomarkers have been observed in the 2019 human pilot trial.
• Nervous System / Gut-Brain Axis: In recent years, the role of Akkermansia muciniphila in neurological diseases has attracted increasing attention. As a probiotic, A. muciniphila is closely associated with host health, metabolism, and immunity, demonstrating therapeutic potential in various conditions including obesity, atherosclerosis, inflammatory bowel disease, diabetes, and liver disorders.
• Oncological / Immune-Oncological: Correlative evidence links higher A. muciniphila abundance with improved responses to anti-PD-1/PD-L1 immunotherapy.

7. Dosage Forms and Dosages Reported in Studies

Human Clinical Trial Dosing

The landmark human clinical trial published in Nature Medicine in 2019 by Depommier and colleagues enrolled 32 overweight, insulin-resistant adults in a randomized, double-blind, placebo-controlled design. Participants received either a placebo, live Akkermansia, or pasteurized Akkermansia daily for three months at a dose of 10 billion CFUs (approximately 10¹⁰ cells/day).

Regulatory Reference Doses

The proposed applicant dose for pasteurized A. muciniphila as a food supplement is a maximum of 5 × 10¹⁰ cells/day by adults, excluding pregnant and lactating women, and in foods for special medical purposes.

Based on literature data, and by applying an uncertainty factor of 200 to the no-observed-adverse-effect level (NOAEL) of a 90-day repeated-dose oral toxicity study in rats, the EFSA Panel concluded that the consumption of 3.4 × 10¹⁰ cells/day is safe for the target population, under the provision that the number of viable cells in the novel food is below the limit of detection (< 10 CFU/g).

For adolescents, EFSA concluded that the novel food is safe at doses up to 2.1 × 10¹⁰ cells/day for adolescents aged 12 to < 14 years, and 3.0 × 10¹⁰ cells/day for adolescents aged 14 years to < 18 years. The safety of the novel food in pregnant and lactating women has not been established.

In 2022, pasteurized A. muciniphila was authorized for placing on the market of the European Union by Commission Implementing Regulation (EU) 2022/168. In 2024, the Food Standards Agency (FSA) and Food Standards Scotland (FSS) completed their risk assessment of pasteurized A. muciniphila in food supplements and Foods for Special Medical Purposes (FSMPs) for the general population from 12 years of age at up to 4 × 10¹⁰ cells/day.

Route and Form

All human studies to date have used oral administration. Commercially available supplements are typically formulated as capsules or powder sachets. Refrigeration or freeze-drying is generally required for stabilization, particularly for live formulations.

8. Safety Considerations and Interactions

General Tolerability

Oral Akkermansia muciniphila, either live or pasteurized, "are safe and well tolerated in overweight and obese individuals." However, its safety for use as a treatment during disease states is unestablished.

EFSA described A. muciniphila as a "well‐characterised non‐toxin producing, avirulent microorganism that has been reported as part of normal gut microbiota" and determined based on a literature review that its safety is adequate for use as a food supplement or in foods for special medical purposes, at a specified maximum dose.

Qualified Presumption of Safety (QPS) Status

A. muciniphila has not yet been granted Qualified Presumption of Safety (QPS) status, largely due to concerns regarding strain-specific variability in antibiotic resistance, potential virulence factors, and limited toxicological data across different formulations.

In 2024, the EFSA Panel on Biological Hazards (BIOHAZ) reassessed the suitability of A. muciniphila for the QPS status. As in the first assessment in 2020, the BIOHAZ Panel considered that the A. muciniphila species is not suitable for QPS status due to safety concerns. The BIOHAZ Panel also noted that conflicting data available in the published literature might be due to colonization of the colon by different A. muciniphila strains, which might produce disparate effects.

Antibiotic Resistance Genes

Although the presence of antibiotic resistance genes (ARGs) must be regarded cautiously considering the worldwide spread of antibiotic resistance challenge, the real concern lies in their transmission across bacterial species. EFSA-FEEDAP guidelines for the evaluation of a novel probiotic strain consider acquired resistance a major safety concern that must be fully addressed in order to obtain authorization for human consumption.

A. muciniphila is thought to be particularly plastic and prone to gaining antimicrobial resistance (AMR). In Europe, information on AMR for bacteria deliberately introduced into the food chain is of paramount importance to declaring a microorganism safe for human and animal consumption.

LPS and Immunological Considerations in Susceptible Populations

Although A. muciniphila is regarded as a highly promising target, its clinical translation faces several safety challenges. As a Gram-negative bacterium, its outer membrane lipopolysaccharide (LPS) could potentially induce excessive inflammation or opportunistic infections in susceptible populations (e.g., immunocompromised patients), yet clinical safety data specific to these high-risk groups are currently lacking.

Furthermore, its mucin-degrading and colonizing properties might exacerbate mucosal damage and increase the risk of bacterial translocation in individuals with pre-existing impairment of the intestinal barrier (e.g., those with active inflammatory bowel disease).

IBD and Active Colitis

Some studies have contradicted the role of A. muciniphila in colitis and inflammatory bowel disease (IBD), which may be attributed to strain differences. The role of strain variability in IBD outcomes is an active area of investigation, and the safety and appropriateness of supplementation during active IBD flares has not been established in controlled human trials.

Elevated Abundance in Certain Neurological Conditions

Some published research has reported elevated A. muciniphila levels in patients with Parkinson's disease and multiple sclerosis, raising questions about whether higher abundance is uniformly beneficial across all disease contexts. The significance of this observation remains under active investigation and the causal direction is not established.

Pregnant and Lactating Women

No evidence was provided for the safety of pasteurized A. muciniphila in pregnant and lactating women. EFSA concluded that the safety of the novel food in pregnant and lactating women has not been established.

Interaction with Antibiotics

Combining live probiotics with concurrent antibiotic use can reduce efficacy significantly, and timing supplementation to avoid antibiotic interference is important. Because A. muciniphila is an obligate anaerobe that is susceptible to many broad-spectrum antibiotics, co-administration with antibiotics would be expected to reduce or abolish any colonization benefit from live preparations. Pasteurized (non-viable) preparations are not subject to antibiotic-mediated killing, but their efficacy as colonizing agents would similarly be absent.

Dietary Modulators of Endogenous Abundance

Because A. muciniphila is a resident commensal organism, its abundance can also be modulated through dietary means without direct supplementation. Dietary polyphenols can distinctly stimulate the relative abundance of A. muciniphila, contributing to the attenuation of several diseases, including obesity, type 2 diabetes, inflammatory bowel diseases, and liver damage. Resveratrol, polyphenols extracted from apple, cranberry, grape, pomegranate, and green tea have shown efficacy in preventing obesity and other metabolic syndromes, accompanied by an increase in the relative abundance of Akkermansia.

Additionally, enrichment of A. muciniphila is frequently observed in individuals or animals undergoing calorie restriction.

References

• Wikipedia – Akkermansia muciniphila
• Nature Reviews Microbiology – Akkermansia muciniphila: biology, microbial ecology, host interactions and therapeutic potential (2024)
• Nature Reviews Gastroenterology & Hepatology – Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms (2022)
• Nature Medicine – Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study (2019)
• PMC – Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study (full text, PMC)
• PubMed – Supplementation with Akkermansia muciniphila in overweight and obese human volunteers (PubMed abstract)
• ScienceDirect – The metabolic, protective, and immune functions of Akkermansia muciniphila (2022)
• PMC – A next-generation beneficial microbe: Akkermansia muciniphila
• PMC – Role of Akkermansia in Human Diseases: From Causation to Therapeutic Properties
• Frontiers in Gastroenterology – Akkermansia muciniphila: The state of the art, 18 years after its first discovery (2022)
• EFSA Journal – Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283 (2021)
• PMC – EFSA Safety Opinion on pasteurised Akkermansia muciniphila as a novel food (2021, open access)
• EFSA – Safety of an extension of use of pasteurised Akkermansia muciniphila as a novel food (2025)
• PMC – Safety of an extension of use of pasteurised Akkermansia muciniphila as a novel food (2025, full text)
• PMC – Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function
• ScienceDirect – Function and therapeutic potential of Amuc_1100, an outer membrane protein of Akkermansia muciniphila: A review (2025)
• Frontiers in Immunology – The role of Akkermansia muciniphila in the regulation of inflammatory bowel disease (2025)
• PubMed – Potential of Akkermansia muciniphila and its outer membrane proteins as therapeutic targets for neuropsychological diseases (2023)
• Frontiers in Microbiology – Potential of Akkermansia muciniphila and its outer membrane proteins as therapeutic targets for neuropsychological diseases (2023)
• PMC – Akkermansia muciniphila and its membrane protein ameliorates intestinal inflammatory stress and promotes epithelial wound healing via CREBH and miR-143/145
• PMC – Akkermansia muciniphila, a New Generation of Beneficial Microbiota in Modulating Obesity: A Systematic Review
• Frontiers in Microbiology – Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems (2020)
• PMC – Big lessons from the little Akkermansia muciniphila in hepatocellular carcinoma (2025)
• PubMed – Landscape of tumoral ecosystem for enhanced anti-PD-1 immunotherapy by gut Akkermansia muciniphila (2024)
• Gut Pathogens – Modulatory role of Akkermansia muciniphila in cancer pathophysiology: a systematic review and meta-analysis of preclinical studies (2026)
• ScienceDirect – Akkermansia muciniphila attenuates high-fat diet-induced atherosclerosis through regulation of the endocannabinoid system (2026)
• Food Frontiers – Therapeutic potential of dietary nutrients and medicinal foods against metabolic disorders: Targeting Akkermansia muciniphila (2024)
• PMC – Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man
• ScienceDirect – Dietary strategies to promote the abundance of intestinal Akkermansia muciniphila, a focus on the effect of plant extracts (2022)
• Frontiers in Immunology – Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases (2024)
• Frontiers in Medicine – The role of Akkermansia muciniphila in maintaining health: a bibliometric study (2025)
• Frontiers in Neuroscience – Akkermansia muciniphila in neurological disorders: mechanisms and therapeutic potential via the gut-brain axis (2025)
• PMC – Akkermansia muciniphila in neurological disorders: mechanisms and therapeutic potential via the gut-brain axis (full text, 2025)
• PMC – Insights into the Antimicrobial Resistance Profile of a Next Generation Probiotic Akkermansia muciniphila DSM 22959
• Scientific Reports – Characterization of antibiotic-resistance traits in Akkermansia muciniphila strains of human origin (2022)
• Microbiology Spectrum – Safety Evaluation and Probiotic Potency Screening of Akkermansia muciniphila Strains Isolated from Human Feces and Breast Milk
• PMC – Strain-Specific Safety Evaluation of Akkermansia muciniphila Akk11: Comprehensive Genotypic, Phenotypic, and Toxicological Assessment
• MDPI Foods – Characterization and Preliminary Safety Evaluation of Akkermansia muciniphila PROBIO (2024)
• MDPI Microorganisms – Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How?
• PMC – Commentary: Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome
• Scientific Reports – Reclassification of eight Akkermansia muciniphila strains (2022)
• ISAPP – Pasteurized Akkermansia muciniphila as a postbiotic: EFSA approval and beyond
• MDPI Fermentation – Response of Akkermansia muciniphila to Bioactive Compounds: Effects on Its Abundance and Activity (2025)