The human gut microbiome is teeming with trillions of microorganisms that all coexist, including bacteria, yeasts, and viruses. Interestingly, the human body has approximately the same number of human cells as bacterial cells. Researchers are beginning to understand how specific bacteria, their metabolites, and syntrophic interactions support human health. Of the trillions of microorganisms present in the gut microbiome, Akkermansia muciniphila (A. muciniphila) and Anaerostipes caccae (A. caccae) are recognized as “next-generation” probiotics that demand attention.  

Akkermansia muciniphila 

A. muciniphila stands out as a keystone species recognized to support the gut and metabolic health of the host. Its role in human health becomes apparent when considering its reduced abundance in patients with prediabetes, type 2 diabetes mellitus (T2DM), obesity, and inflammatory bowel disease (IBD), compared to healthy controls. As the name implies, this bacterium is “mucin-loving” and utilizes and degrades the mucus layer of the intestines as its primary energy source.  

This characteristic is central to how A. muciniphila supports gut barrier integrity. Interestingly, its mucin-degrading properties have been shown in animal models to directly and indirectly stimulate the regeneration of mucus-producing cells, called goblet cells, which help maintain gut barrier integrity. Additionally, this bacterium also produces short-chain fatty acids (SCFAs), such as acetate and propionate, which fuel the growth of butyrate-producing bacteria, including A. caccae and Faecalibacterium prausnitzii (F. prausnitzii). Butyrate is then utilized as the primary source of energy for driving enterocyte growth and proliferation. Healthy SCFA production supports gut health by reducing intestinal pH, inhibiting the overgrowth of potentially pathogenic bacteria, and promoting healthy inflammatory responses, making A. muciniphila a critical player in shaping a diverse gut ecosystem.  

Emerging research also highlights A. muciniphila’s influence on healthy blood glucose metabolism and body composition. In both animal and human studies, higher abundance of A. muciniphila has been associated with improved glucose metabolism, enhanced GLP-1 production, and improvements in body composition and low-density lipoprotein (LDL) cholesterol. These effects may stem from the bacteria’s SCFA production, and a secreted protein called P9, which supports GLP-1 secretion — an important hormone involved in normal insulin metabolism and appetite regulation.  

A. muciniphila is available in both live and heat-killed (pasteurized) forms. Heat-killed preparations, often referred to as postbiotics, retain outer membrane proteins, such as Amuc_1100, which may still support immune health. However, live A. muciniphila offers ongoing mucus fermentation, which fuels SCFA production and supports microbial cross-feeding processes essential for promoting gut barrier integrity. Overall, A. muciniphila stands out as a next-generation probiotic with multifaceted benefits for maintaining gut integrity, modulating the immune system, and enhancing metabolic function. 

Anaerostipes caccae  

While A. muciniphila plays a foundational role in breaking down mucin and producing metabolites like acetate, its benefits are amplified through its partnership with other beneficial microbes, such as the butyrate-producer A. caccae. This next-generation bacterium was originally isolated and designated as the type species (meaning first and defining member) of its genus Anaerostipes in 2002. Within the Bacillota (formerly Firmicutes) phylum, A. caccae belongs to the Clostridium coccoides group (also known as Clostridium cluster XIVa) which is known for supporting butyrate production and host immune health.

Butyrate is a key SCFA that plays an integral role in gut health. It supports colon and mucosal health by nourishing colonocytes and promoting gut barrier integrity and healthy inflammatory responses. Colonocytes absorb butyrate and oxidize it in their mitochondria, producing CO₂ and ATP, which accounts for 70% to 80% of their energy supply, fueling essential functions like electrolytes transport and intestinal barrier support. Butyrate also promotes the integrity of the intestinal epithelial barrier by supporting tight junctions and the mucus layer. This important SCFA may also play an important role in promoting gastrointestinal (GI) regularity by enhancing colonic motility and maintaining gut homeostasis.

The mechanism by which A. caccae promotes direct butyrate production is linked to its metabolic flexibility – it is capable of both primary carbohydrate fermentation and secondary cross-feeding. A. caccae can directly ferment various dietary carbohydrates, including glucose, fructose, sucrose, and prebiotic fibers, using the glycolytic and acetyl-CoA pathways, to deliver butyrate in the lower GI tract. Additionally, A. caccae has been shown to ferment mucin-derived sugars such as glucose, mannose, galactose, and N-acetylgalactosamine, made by the mucin-degrading bacteria A. muciniphila, to produce butyrate, acetate, and lactate. 

A. caccae can also cross-feed on the lactate and acetate produced by other bacteria, such as  A. muciniphila and other carbohydrate-fermenting bacteria like Bifidobacterium and Lactobacillus species. Interestingly, A. caccae can convert both the l-lactate produced by Bifidobacterium species and the d-lactate produced by Lactobacillus species, potentially playing an important role in mitigating lactate buildup and supporting a balanced microbial ecosystem. The cross-feeding conversion utilizes the acetyl-CoA pathway in which lactate is first oxidized to pyruvate and then converted to acetyl-CoA, which directly contributes to butyrate synthesis or interconverts with exogenous acetate to produce butyrate.

A. caccae is an anaerobic bacterium supporting epithelial hypoxia, which is essential for maintaining a healthy gut microbial environment by limiting the expansion of opportunistic bacteria and promoting other butyrate producers. It is also spore-forming, which facilitates its transit to the lower intestines. A. caccae is primarily found in the lumen of the lower GI tract, especially the colon, where it thrives in the anaerobic, fiber-rich environment and contributes to the production of butyrate. Butyrate targeted to the lower GI tract (bypassing the upper intestines where it could otherwise be absorbed too early to support colon health) has been shown to promote GI barrier integrity, healthy inflammatory and immune responses, and microbiome diversity. 

The relationship between Akkermansia muciniphila and Anaerostipes caccae 

Both A. caccae and A. muciniphila are next-generation probiotics that warrant attention. However, they may be even more supportive together. Coculture studies involving both bacteria show that A. caccae may improve microbial community metabolic interactions, which may leave fewer resources available to opportunistic bacteria and promote beneficial commensal bacteria, like A. muciniphila. Overall, there seems to exist a symbiotic cross-feeding at the intestinal mucus layer between A. caccae and A. muciniphila. The byproducts of the mucin-degrading A. muciniphila are utilized by neighboring bacteria, like A. caccae, to produce butyrate. In turn, the butyrate produced by A. caccae supports a stable microbial ecosystem that benefits other keystone species, like A. muciniphila. This mutually beneficial interaction highlights the potential of using A. caccae and A. muciniphila in combination to help support GI and microbiome health.

Learn more about commensal species, SCFAs, and the gut microbiome:

Role of Probiotics and Resistant Starch for Healthy Aging

Short-Chain Fatty Acids: What Are They and How Do They Support the Gut-Brain Axis?

Randomized Control Trial Explores Efficacy of Prebiotics for Adults With Occasional Constipation

By Bri Mesenbring, MS, CNS, LDN, and Antonia Toupet, PhD