The genera Lactobacillus and Bifidobacterium have long been the workhorses for traditional research into the health benefits of probiotics and are the most common commercialized probiotics. Now, newer techniques of analyzing microbial communities are leading to the identification of novel microbes, some with probiotic potential. These “next-generation probiotics” (NGPs) may offer unique benefits from more established probiotic strains and hence are an area of intense research. While there are many promising NGPs, this blog will explore one in particular: Akkermansia muciniphila.
Next-Generation Probiotics, in brief
Most of the vast array of microorganisms in the human gut has remained unidentified because they are typically anaerobic bacteria that are difficult to cultivate. Recent advances in microbiology— complete genome sequencing, culture techniques, and bioinformatics— have enabled the precise identification and detection of these bacteria, facilitating the development of NGPs with promising health benefits. Examples include Roseburia intestinalis, Eubacterium spp., Faecalibacterium prausnitzii, Bacteroides spp., and Akkermansia muciniphila. Their selection is often prompted by their correlation to health or, their absence, to disease. Although cause and effect often remain to be documented. Turning these species into industrial probiotics is challenging due to their need for specific growth factors and anaerobic conditions, which increase costs and complexity. Another hurdle is the regulatory approval of new probiotic species without a history of use. However, novel regulatory frameworks are emerging, for example, theLive Biotherapeutic Productscategory being defined by the United States Food and Drug Administration (FDA)and the European Directorate for the Quality of Medicines.
Despite these challenges, Akkermansia muciniphila (A. muciniphila) is a particularly promising candidate.
Akkermansia muciniphila
Isolated just two decades ago, A. muciniphila is a commonly found commensal bacterium that constitutes 1 to 4% of the gut microbiota in healthy individuals. With its ability to live in the mucous layer of the intestine, A. muciniphila plays a crucial role in gut integrity maintenance thereby reducing the abundance of pathogens. It degrades intestinal mucins and glycoproteins for use as energy interacting with host metabolic processes. A. muciniphilacan also increase the production of mucin, which leads to strengthening of the intestinal barrier.
Abundant in the first year of life, A. muciniphila generally decreases with age but was found to be higher in a study with centenarians. Notably, abundance is associated with healthy aging while being reduced in individuals with comorbidities linked to unhealthy aging.
Mechanisms of action
Research has identified three main actions of A. muciniphila: enhancing gut barrier integrity, improving metabolic health, and modulating the immune system. Together or separately, these mechanisms may have implications in diseases; the primary areas of study follow.
Gut disease
Alterations in intestinal barrier permeability, such as changes in tight junction proteins, are associated with the development of inflammatory bowel disease (IBD). A. muciniphila levels are significantly reduced in patients with ulcerative colitis and Crohn’s disease, and its abundance inversely correlates with inflammation.
One recent study investigated the effects of pasteurized A. muciniphila on alleviating IBS-like symptoms and related behavioral disorders in mice, finding that it significantly reduced colonic hypersensitivity, improved gut barrier function, and enhanced anxiety-like behavior and cognitive performance without significantly altering fecal microbiota composition.
A 2024 review of studies suggested that A. muciniphila supplementation may help reduce inflammation and improve gut health, although further research is needed to fully understand its therapeutic potential.
Metabolic disease
Numerous studies highlight the significance of the microbe A. muciniphila in metabolic health. For example, reduced levels of A. muciniphila are linked to diabetes in mice. In addition, a lower fecal abundance has been observed in obese patients with type II diabetes, hypertension, and liver disorders.
A. muciniphila has shown benefit in the following ways:
Improving gut integrity by enhancing gut barrier function, reducing permeability and endotoxemia.
Supporting immune function by enhancing immune signaling, promoting a balanced immune response, and reducing systemic inflammation. It decreases the levels of pro-inflammatory cytokines and markers, thereby alleviating systemic and gut inflammation.
Improving metabolic parameters: Many animal studies report a significant beneficial effect ofA. muciniphilaon the development of diabetes of both types and in obesity management. Supplementation was observed to lead to reduced plasma insulin levels, decreased body fat, and improved metabolic parameters. Most studies used animal models, but a clinical trial with 40 overweight or obese subjects showed that 3 months of A. muciniphila supplementation, both live and pasteurized, significantly reduced plasma insulin and improved insulin sensitivity compared to placebo. Pasteurized A. muciniphila also lowered cholesterol, triglycerides, body weight, fat mass, and waist and hip circumference.
Protecting against liver damage by reducing liver enzymes and guarding against liver fibrosis and non-alcoholic fatty liver disease in mice.
Cancer
With its crucial role in gut integrity, A. muciniphila may guard against permeability that allows toxic and pro-inflammatory substances to penetrate which can lead to carcinogenesis.
A study on immunocompetent mice with prostate cancer found that treatment with extracellular vesicles from A. muciniphila significantly slowed tumor growth, increased tumor-fighting immune cell activity, and showed no toxicity to healthy tissues.
In colorectal cancer, A. muciniphila showed potential in reducing tumor growth and improving immune response in mouse models. Notably, treatments with A. muciniphila have demonstrated enhanced efficacy of colorectal cancer therapies, such as certain chemotherapies, by increasing beneficial immune cell activity and decreasing tumor proliferation without significant toxicity.
A comprehensive review cited the studies pointing to high levels of A. muciniphila in the gut microbiota of lung or kidney cancer patients correlating with a positive response to immunotherapy whereas the absence of this bacterium leads to no such response, a finding supported by fecal transplant studies in mice and further linked to better outcomes in immune checkpoint inhibitor treatments. Thus, A. muciniphila positively affects the response to certain immunotherapy and chemotherapy agents. Most studies are in animals, so further human research is needed.
Neurodegenerative diseases
A. muciniphilais considered integral to brain function via the gut-brain axis. Its safeguarding the intestinal mucosal barrier, modulation of the immune system and production of metabolites, such as short-chain fatty acids, amino acids, and amino acid derivatives suggests therapeutic potential in several neurodegenerative disorders, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple sclerosis (MS).
Alzheimer’s disease
In AD mouse models, a decrease in A.muciniphila is linked to intestinal barrier impairment and cognitive deficits, and supplementation can improve gut health and reduce amyloid-β deposition, enhancing cognitive function. However, human study results regarding the effects ofA. muciniphilahave been inconsistent.
Amyotrophic lateral sclerosis
A. muciniphila is negatively associated with ALS, with decreasing abundance in ALS mice. Research found that its supplementation in an ALS mouse model improved motor function and brain atrophy through nicotinamide accumulation, which supports neuronal health.
Parkinson’s disease
Gut dysbiosis, with an enrichment of A. muciniphila, is observed in both the human prodromal phase of PD and certain PD mouse models, suggesting its role in PD pathogenesis and potential as an early biomarker. While A. muciniphila may contribute to gut inflammation and systemic issues through mucin degradation, it also has anti-inflammatory effects, though its impact on cognitive decline in PD remains uncertain.
Multiple sclerosis
Research indicates that A.muciniphila abundance is significantly higher in MS patients, correlating with a pro-inflammatory T-cell profile that worsens immune response. However, other findings suggest that A. muciniphila may also have beneficial effects, such as reducing the severity of autoimmune encephalomyelitis (the body’s immune system mistakenly attacks the brain and spinal cord) and promoting an anti-inflammatory immune response, suggesting a strain-specific role in MS.
Neuropsychiatric conditions
Research suggests that A.muciniphila may influence neuropsychiatric disorders through its effects on the gut-brain axis, contributing to reduced intestinal imbalances and inflammation. Studies in animal models indicate that supplementation with A. muciniphila can alleviate depressive symptoms and improve mucosal barrier function, potentially enhancing behavioral outcomes and neurochemical profiles. Additional research highlights its potential role in conditions like autism spectrum disorders, where alterations in gut microbiota composition may impact gastrointestinal and neurological function.
Takeaway
A. muciniphila, a gut bacterium isolated two decades ago, plays a crucial role in maintaining gut integrity by living in the intestinal mucous layer and reducing pathogen abundance. It shows promise in improving gut barrier function, enhancing metabolic health, and modulating the immune system, with potential benefits for conditions like inflammatory bowel disease, diabetes, certain cancers, and neurodegenerative and neuropsychiatric disorders. While studies indicate potential therapeutic effects on Alzheimer’s, Parkinson’s, and depressive symptoms, results have been inconsistent, highlighting the need for further research to fully understand its benefits and applications. Partly, these inconsistencies may be explained by strain differences within the species. Despite challenges in industrial production and regulatory approval, A. muciniphila is a focal point of probiotic research due to its significant therapeutic potential across a range of diseases. As many of the studies were conducted in animals, future research in humans should better define its practical potential in health and disease.
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