Akkermansia muciniphila
Akkermansia muciniphila is a gram-negative, anaerobic bacterium in the human gut, thriving in the mucus layer. It degrades mucin, producing short-chain fatty acids that support gut health, reduce inflammation, and improve metabolic function. Comprising 1-5% of healthy gut microbiota, it’s linked to better glucose control and lower obesity risk. Low levels are associated with metabolic disorders.
Benefits
Gut Barrier Integrity
Akkermansia strengthens the gut lining by producing mucin, reducing "leaky gut" and inflammation, which may protect against conditions like irritable bowel syndrome and inflammatory bowel disease.
Metabolic Health
It’s associated with improved insulin sensitivity, glucose regulation, and reduced risk of type 2 diabetes. Studies show higher Akkermansia levels correlate with lower body fat and better weight management.
Weight Management
Akkermansia may help prevent obesity by regulating fat storage and energy metabolism. Clinical trials suggest it reduces visceral fat and supports weight loss when combined with a healthy diet.
Anti-Inflammatory Effects
By reducing systemic inflammation, it may lower the risk of chronic diseases like cardiovascular disease and metabolic syndrome.
Immune Support
It interacts with the immune system, promoting a balanced response and potentially reducing autoimmune-related issues.
Potential Mental Health Benefits
Emerging research suggests a gut-brain axis link, where Akkermansia may influence mood and cognitive function by reducing inflammation and supporting neurotransmitter pathways.
Mechanism of Action
Mucin Degradation and Gut Barrier Enhancement
Akkermansia resides in the gut mucus layer and uses mucin (a glycoprotein in the intestinal lining) as an energy source. By degrading mucin, it stimulates goblet cells to produce more mucus, thickening the gut barrier and reducing permeability ("leaky gut"). This strengthens intestinal integrity, preventing harmful substances like endotoxins (LPS) from entering the bloodstream, which reduces systemic inflammation.
Production of Short-Chain Fatty Acids (SCFAs)
Akkermansia ferments mucin and dietary fibers, producing SCFAs like acetate and propionate. SCFAs serve as energy for colon cells, regulate appetite by signaling satiety hormones (e.g., GLP-1, PYY), and improve insulin sensitivity by activating pathways like AMPK in liver and muscle tissues.
Modulation of Lipid Metabolism
Akkermansia reduces fat absorption and storage by regulating bile acid metabolism in the gut. It promotes the expression of genes involved in fatty acid oxidation (e.g., PPAR-α), decreasing visceral fat accumulation and improving cholesterol profiles.
Anti-Inflammatory Effects
It reduces circulating levels of lipopolysaccharides (LPS), which trigger inflammation via TLR4 signaling. Akkermansia enhances the production of anti-inflammatory cytokines (e.g., IL-10) and interacts with immune cells like regulatory T-cells to dampen inflammatory responses.
Interaction with Host Receptors via Amuc_1100
A key protein, Amuc_1100, found in Akkermansia’s outer membrane, interacts with TLR2 receptors on gut epithelial and immune cells. This interaction activates signaling pathways that improve gut barrier function, insulin sensitivity, and immune homeostasis. Amuc_1100 remains active even in pasteurized forms of Akkermansia, contributing to its therapeutic potential.
Gut-Brain Axis Modulation
By reducing inflammation and producing metabolites like SCFAs, Akkermansia may influence the gut-brain axis, potentially affecting neurotransmitter production (e.g., serotonin) and stress responses via the vagus nerve.
Clinical Trials
Supplementation with Akkermansia muciniphila in Overweight and Obese Human Volunteers: A Proof-of-Concept Exploratory Study
Study: A randomized, double-blind, placebo-controlled pilot study conducted by Depommier et al. in 2019 enrolled 40 overweight or obese insulin-resistant adults, with 32 completing the trial. Participants received daily oral supplementation with either live A. muciniphila (10^9 or 10^10 CFU), pasteurized A. muciniphila (10^10 cells), or placebo for 3 months. The primary endpoints were safety, tolerability, and metabolic parameters, including insulin resistance, circulating lipids, visceral adiposity, and body mass. The study also assessed GLP-1-related outcomes indirectly through metabolic improvements.
Findings: Pasteurized A. muciniphila significantly improved insulin sensitivity (HOMA-IR reduced) and reduced insulinemia compared to placebo. It also slightly decreased body weight (−2.27 ± 0.92 kg, P = 0.091), fat mass (−1.37 ± 0.82 kg, P = 0.092), and hip circumference (−2.63 ± 1.14 cm, P = 0.091) compared to baseline. Live A. muciniphila showed similar but less pronounced effects. The study confirmed safety and tolerability, with no adverse effects reported. GLP-1 was not directly measured, but improvements in insulin sensitivity and glucose metabolism suggest enhanced GLP-1 signaling, likely mediated by A. muciniphila’s production of SCFAs (e.g., propionate), which stimulate GLP-1 secretion via GPR41/43 receptors on L-cells. Pasteurized A. muciniphila was more effective than live cells, potentially due to the stability of the Amuc_1100 protein, which interacts with TLR2 to enhance gut barrier function and metabolic signaling.
Link: Nature Medicine - Supplementation with Akkermansia muciniphila in Overweight and Obese Human Volunteers
Randomized Trial Assessing Impact of Probiotic Supplementation on Gut Microbiome and Clinical Outcome from Targeted Therapy in Metastatic Renal Cell Carcinoma
Study: Conducted by Dizman et al. in 2021, this randomized trial evaluated the impact of probiotic supplementation, including A. muciniphila, on the gut microbiome and clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) receiving targeted therapy. The study included a probiotic cocktail and assessed gut microbiota composition and treatment response.
Findings: Patients receiving probiotics showed a higher abundance of A. muciniphila in their gut, which was significantly associated with improved clinical outcomes from targeted therapy. While GLP-1 levels were not directly measured, the increased A. muciniphila abundance likely contributed to enhanced metabolic and immune responses, potentially via SCFA-mediated GLP-1 secretion, which supports immune modulation and metabolic health. The study highlights A. muciniphila’s role in improving therapeutic efficacy, possibly through gut barrier enhancement and immune system regulation.
Link: Cancer Medicine - Randomized Trial Assessing Impact of Probiotic Supplementation
Effect of Sodium Butyrate and Inulin Supplementation on Akkermansia muciniphila Abundance in Type 2 Diabetes
Study: A randomized, double-blind, placebo-controlled trial by Roshanravan et al. (published in 2020) investigated the effects of sodium butyrate and inulin supplementation on gut microbiota, including A. muciniphila, in patients with type 2 diabetes. The study focused on metabolic outcomes and angiotensin signaling, with A. muciniphila abundance as a key variable.
Findings: Supplementation with sodium butyrate and inulin significantly increased A. muciniphila abundance, which was associated with improved glycemic control and reduced angiotensin signaling. The increase in A. muciniphila likely enhanced GLP-1 secretion through SCFA production (e.g., butyrate and propionate), which activates GPR41/43 receptors on L-cells, leading to improved insulin sensitivity and glucose homeostasis. The study supports A. muciniphila’s role as a therapeutic target for type 2 diabetes management, with indirect evidence of GLP-1 modulation.
Link: Frontiers in Akkermansia muciniphila in Maintaining Health
Akkermansia muciniphila Clinical Trial for Glucose and Cholesterol Reduction
Study: An ongoing clinical trial by Vidya Herbs (reported in 2024) evaluates the efficacy of A. muciniphila (10 BCFU) supplementation on fasting blood sugar, HbA1c, lipid levels, insulin sensitivity, BMI, body weight, waist circumference, and physical performance in human volunteers. The trial aims to validate A. muciniphila’s therapeutic potential for metabolic health, with a focus on glucose and cholesterol reduction.
Findings: Preliminary data suggest A. muciniphila supplementation improves fasting blood sugar, lipid profiles, and insulin sensitivity, likely through GLP-1 stimulation via SCFA production and Amuc_1100-mediated TLR2 signaling. Specific results on GLP-1 levels are not yet published, but the trial builds on prior evidence linking A. muciniphila to enhanced GLP-1 secretion and metabolic benefits. The study incorporates a novel encapsulation technology to ensure A. muciniphila stability, enhancing its potential for clinical application.
Link: NutraIngredients-USA - Akkermansia muciniphila: Promising New Human Clinical Trials for Probiotics
Gut Microbiota Modulation through Akkermansia spp. Supplementation Increases CAR-T Cell Potency
Study: A 2025 study by Marcos-Kovandzic et al., published in Cancer Discovery, explored the effects of A. muciniphila supplementation on the gut microbiota and chimeric antigen receptor (CAR) T-cell therapy potency in cancer patients. The study assessed how A. muciniphila modulates the gut microbiome to enhance immunotherapy outcomes.
Findings: Supplementation with Akkermansia spp. increased the abundance of A. muciniphila, which was associated with enhanced CAR-T cell potency and improved clinical responses. While GLP-1 was not directly measured, A. muciniphila’s role in producing SCFAs likely contributed to immune modulation and metabolic improvements, potentially via GLP-1 pathways, as SCFAs are known to stimulate GLP-1 secretion. The study suggests A. muciniphila as a potential adjuvant for immunotherapy, with metabolic benefits supporting overall health.
Link: Cancer Discovery - Gut Microbiota Modulation through Akkermansia spp. Supplementation
Potential Side Effects
Digestive Discomfort
When starting Akkermansia supplementation, some individuals may experience mild gastrointestinal symptoms, including: Bloating, Gas, Nausea and Loose stools or mild diarrhea.
Changes in bowel habits
These symptoms are typically temporary, resolving within the first 14 days as the gut microbiome adjusts. Starting with a lower dose and gradually increasing it may help manage these effects.
Microbial Balance Shifts
Akkermansia can alter the gut’s microbial composition, affecting populations of other bacteria (e.g., Firmicutes and Bacteroidetes). This shift may influence digestion and metabolism, potentially causing transient changes in stool consistency or gut motility.