Akkermansia Muciniphila is Associated with Human Health: What Should we Know?

Akkermansia muciniphila was first isolated from the faeces of a healthy adult Caucasian female in 2004 as the first known member of the Akkermansia genus and the only isolated member of the Verrucomicrobiota phylum (Derrien et al. 2004). The anaerobic, Gram-negative, non-motile, and non-spore-forming bacterium colonizes the intestines and nasopharynx of humans and other animals (Derrien et al. 2004). Other environments it inhabits include the appendix, the pancreas (in pathological conditions), human breast milk, and human blood samples (Geerlings et al. 2017). Since then, other members of the genus have been found inhabiting the human gut (Kobayashi et al. 2018). Akkermansia is a genus that has recently attracted much attention due to its probiotic effects and possible role in bowel disease treatment (approved by the European Food Safety Authority (EFSA).

A. muciniphila is an early colonizer of the human gut that reaches an abundance similar to or slightly lower than that in adults within the first year of life and then decreases in the elderly. The abundance appears to be higher in formula-fed than in breast-fed infants, and increases once breast-feeding stops (Azad et al. 2018). A Chinese study found a colonization rate of 51-74% in southern China and identified 22 strains within the studied population (Guo et al. 2016). Abundance and colonization rate can vary between countries, and the composition of the microbiota is influenced by diet and genetic factors (Grześkowiak et al. 2012). Nonetheless, the consensus is that A. municiphila is a common and stable part of the human gut microbiota. A. municiphila growth can be stimulated by diet, with one study demonstrating that dietary polyphenols from grapes can dramatically promote its growth in mouse models (Roopchand et al. 2015). Another study demonstrated that fucoids from brown seaweed increased the abundance of Akkermansia in mice with metabolic syndrome induced by a high-fat diet (Qingsen et al. 2017).

One of the key characteristics of A.muciniphila is the ability to degrade mucins and use them as an energy source. Mucins are high-molecular-weight glycoproteins continuously secreted by goblet cells, which constitute a significant component of the intestinal mucus and form the protective mucus layer. Of the 21 different mucins identified, mucin 2 (MUC2) is the predominant component of the colonic mucus layer and acts as its structural skeleton (Song et al. 2023). The mucus layer serves as the first line of defense, protecting the epithelium from inflammation and infection. Disruption of the mucus layer is an important factor in the development of intestinal diseases, including inflammatory bowel disease (IBD) and colorectal cancer. The mucus barrier maintains homeostasis by stimulating the growth of appropriate microbiota and preventing pathogens from contacting the epithelium (Song et al. 2023).

Mucin-degrading bacteria produce glycosyl hydrolases (GHs), specialized enzymes that enable them to break down mucins. The A. muciniphila genome contains genes encoding nine different GH families (Glover et al. 2022). It can utilize different combinations to hydrolyze up to 85% of mucin structures, allowing it to use mucins as its sole carbon source (Glover et al. 2022). As a result, A. muciniphila is often considered one of the most important mucin degraders in the human microbiota. The metabolism of mucins by A. muciniphila, in addition to the action of other bacterial species, releases monosaccharides, oligosaccharides, and short-chain fatty acids into the intestinal environment, thereby contributing to the modulation of intestinal homeostasis (Belzer et al. 2012). Although A. muciniphila degrades mucin, it does so in a controlled and selective manner, which (1) stimulates the production of new, healthy mucus, (2) supports the regeneration of the mucus and epithelial barrier, and (3) reduces inflammation and strengthens mucosal immunity (Si et al. 2022). As such, its presence in the gut microbiota is associated with better metabolic, immune, and barrier health (Table 1).

The primary reported benefits of A. muciniphila are associated with alleviating symptoms or preventing gastrointestinal disease, with a primary focus on Inflammatory Bowel Disease IBD. IBD refers to a group of diseases that cause inflammation of the bowel, with the primary types being ulcerative colitis (UC) and Crohn’s disease (CD). Symptoms may include diarrhea, abdominal pain, fatigue, nausea, and weight loss. Significant evidence suggests a correlation between A. muciniphila and the development of IBD, although its nature remains under discussion. In a mouse study, treatment with A. muciniphila for five weeks reduced inflammation caused by chemically induced colitis (Yilmaz et al. 2024). Another mouse model found that A. muciniphila improved clinical parameters, including spleen weight, colon inflammation index, colon histological score, and regulation of pro-inflammatory cytokines, with varying activity levels among strains (Zhai et al. 2019). In addition, A. muciniphila supplementation reduced serum and tissue inflammatory cytokines and chemokines in mice, along with reduced weight loss, improved histological scores, and enhanced barrier function (Bian et al. 2019).

The role of A. muciniphila in the prevention of IBD can be inferred from its reduced presence in IBD patients, with UC and CD exhibiting lower colonization rates and abundance compared to healthy individuals, both of which increase significantly after washed microbiota transplantation (Qu et al. 2021). Additionally, A. muciniphila was lower in patients with active UC compared to those with quiescent UC and healthy individuals (Zhang et al. 2020). The same study identified a reduction of sulfated mucins in the mucus of IBD patients as a potential cause of A. muciniphila reduction (Zhang et al. 2020).

Investigations into the mechanisms underlying the anti-inflammatory effects of A. muciniphila are ongoing. Aside from the well-known anti-inflammatory effects of short-chain fatty acids (SCFA) produced by the human microbiota, there have been reports that one of the main surface proteins of A. muciniphila (Amuc_1100) could play a crucial role (Wu et al. 2019).

The anti-inflammatory effect of A. muciniphila might also be beneficial for patients with Parkinson’s disease (PD). Indeed, an A. muciniphila treatment alleviated artificially induced PD in mice, including neuroinflammation and motor dysfunction, while promoting neurogenesis (Qiao et al. 2024). However, the evidence for the beneficial effects of A. muciniphila remains inconclusive, with some reports not aligning with the previously mentioned results. One such study detected an increase in A. muciniphila in patients with colorectal cancer (Weir et al. 2013), suggesting that the relationship between A. muciniphila and host health might be more complex.

Another area in which A. muciniphila is heavily investigated for its beneficial effects is obesity, with the bacterium’s anti-obesity effects demonstrated in several studies. An analysis of data from the American Gut Project has found an association between a higher abundance of A. muciniphila and a lower risk of obesity (Zhou et al. 2020). A randomized controlled trial reported that A. muciniphila supplementation reduced obesity, though the effects appear to be limited to individuals with a low baseline abundance of the bacterium (Zhang et al. 2025). In this regard, the reduction of A. muciniphila was associated with the development of atherosclerosis induced by a high-fat Western diet in apolipoprotein E knock-out mice (Li et al. 2016). Meanwhile, daily administration of A. muciniphila has been shown to prevent weight gain, hyperphagia, and dysglycemia caused by the dietary emulsifiers carboxymethylcellulose and polysorbate (Daniel et al. 2023).

Investigations into the anti-obesity mechanisms of A. muciniphila demonstrated that the species can alleviate the negative effects of interferon gamma (IFNɣ) on glucose tolerance (Greer et al. 2016). Another potential mechanism of action involves Amuc_1100, which has some of the same effects as the live bacterium when purified or applied as part of pasteurized A. muciniphila (Anhê et al. 2017). It is very likely that the effects of A. muciniphila on obesity are not centred on a single mechanism, but result from several separate effects in conjunction with other members of the human gut microbiota. Furthermore, many studies have involved mice fed a high-fat diet, so the impact on different sources of obesity should still be investigated.

As described previously, A. muciniphila has several potential benefits for human health. However, it is worth discussing whether it can be used as a probiotic. Aside from providing health benefits to the host, a good probiotic should be considered safe for human consumption, and it should be able to survive long enough in storage and after consumption to reach the gut. A toxicological analysis of pasteurized A. muciniphila did not reveal any mutagenic, clastogenic, or aneugenic effects, nor did it reveal any adverse neurobehavioural or pathological effects that would undermine its use as a food additive (Druart et al. 2021). A comparative analysis of A. muciniphila and the commonly used probiotic bacterium Lactobacillus rhamnosus GG revealed comparable levels of auto-aggregation, co-aggregation, hydrophobicity, and antimicrobial activity, but a higher level of antibiotic resistance in A. muciniphila. It is generally recommended that probiotic bacteria have a low level of antibiotic resistance to prevent potential horizontal gene transfer. However, the presence of resistance genes associated with transferable genetic elements has not been reported in A. muciniphila (Cozzolino et al. 2020).

Methods for cultivating A. muciniphila have improved since its initial discovery. Using mucin in growth medium is costly and inconvenient, so the use of alternatives has been investigated. One study identified glucose or N-acetylglucosamine (a component of mucins) as a good source of carbon, and tryptone as a reliable source of nitrogen (Wu et al. 2024). Another study identified galactose, sialic acid, lactose, and chitosan as factors significantly promoting A. muciniphila growth (Meng et al. 2024).

A. muciniphila supplementation provides significant benefits for patients suffering from IBD. Its relationship with obesity seems to be more complex, though studies agree that it alleviates symptoms associated with a high-fat diet, which is common in Western countries. As a natural member of the human microbiota, A. muciniphila is generally considered safe, which is supported by evidence, and has been approved by EFSA. There are also no technical obstacles to its use as a commercial probiotic. A. muciniphila’s general functions are summarised in Figure 1.

Figure1.

Summary of the role of A.muciniphila in health and disease. Illustration created using Biorender (www.biorender.com). Agreement number: CA28PV7H2E