Adaptation of Akkermansia muciniphila to the Oxic-Anoxic Interface of the Mucus Layer

Abstract

Akkermansia muciniphila colonizes the mucus layer of the gastrointestinal tract, where the organism can be exposed to the oxygen that diffuses from epithelial cells. To understand how A. muciniphila is able to survive and grow at this oxic-anoxic interface, its oxygen tolerance and response and reduction capacities were studied. A. muciniphila was found to be oxygen tolerant. On top of this, under aerated conditions, A. muciniphila showed significant oxygen reduction capacities and its growth rate and yield were increased compared to those seen under strict anaerobic conditions. Transcriptome analysis revealed an initial oxygen stress response upon exposure to oxygen. Thereafter, genes related to respiration were expressed, including those coding for the cytochrome bd complex, which can function as a terminal oxidase. The functionality of A. muciniphila cytochrome bd genes was proven by successfully complementing cytochrome-deficient Escherichia coli strain ECOM4. We conclude that A. muciniphila can use oxygen when it is present at nanomolar concentrations. IMPORTANCEThis article explains how Akkermansia muciniphila, previously described as a strictly anaerobic bacterium, is able to tolerate and even benefit from low levels of oxygen. Interestingly, we measured growth enhancement of A. muciniphila and changes in metabolism as a result of the oxygen exposure. In this article, we discuss similarities and differences of this oxygen-responsive mechanism with respect to those of other intestinal anaerobic isolates. Taken together, we think that these are valuable data that indicate how anaerobic intestinal colonizing bacteria can exploit low levels of oxygen present in the mucus layer and that our results have direct relevance for applicability, as addition of low oxygen concentrations could benefit the in vitro growth of certain anaerobic organisms.T he gastrointestinal (GI) tract harbors a rich and diverse microbial community, which has proven to play a role in host health and physiology (1). This microbial community is not in direct contact with epithelial cells; a thin layer of host-derived mucus separates them. The outer layer of mucus is colonized with microbes that differ in composition from the luminal microbiota (2, 3). The mucin glycans are used by some bacteria as growth substrates, resulting in the production of short-chain fatty acids (SCFAs) (4). To the host, the SCFAs are important modulators of gut health (4). To the microbial community, SCFAs are a necessary waste product, and the process of SCFA production is required to maintain the redox balance in the cell, as it can restore the NAD ϩ /NADH ratio (5). One member of the mucosa-associated microbiota is Akkermansia muciniphila, a mucin-degrading specialist that can use mucin as a sole carbon and nitrogen source (6). A. muciniphila is associated with a healthy GI tract, as its abundance is inversely correlated with several GI tract-related disorders (7). Moreover, it has been shown that A. muciniphila has immune-stimulatory capacities, stimul...

Complete Genome Sequence of Akkermansia glycaniphila Strain Pyt T , a Mucin-Degrading Specialist of the Reticulated Python Gut

“…The Pyt T genome is predicted to encode a cytochrome bd ubiquinol oxidase, indicating the potential for aerobic respiration. This bacterium might use this in the oxic-anoxic interface of its probable habitat: the intestinal mucin layer, as recently has been experimentally verified for A. muciniphila Muc T (14). …”

Effect of Vegan Fecal Microbiota Transplantation on Carnitine‐ and Choline‐Derived Trimethylamine‐N‐Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome

“…In contrast, autologous FMT affected the relative abundance of bacterial genera related to A faecalis and Akkermansia , with the latter related to beneficial metabolic health . Although the mechanism is unclear, it might be that the aerobic treatment of autologous feces has selected the oxygen‐tolerant Akkermansia and A faecalis . These bacterial strains may subsequently occupy the niche in the fecal microbiota that was created by eradication of other anaerobic species.…”

Model‐driven design of a minimal medium for Akkermansia muciniphila confirms mucus adaptation

“…In addition to the degradation of intestinal mucins, A. muciniphila was shown to be closely associated to colonic epithelial cells producing these mucins (Derrien et al ., ). The adaptation to this niche is exemplified by the capabilities of A. muciniphila to utilize low concentrations of oxygen present in the mucus layer (Ouwerkerk et al ., ), even though it was previously characterized as a strictly anaerobic bacterium (Derrien et al ., (Derrien et al ., ). The efficient use of mucin by A. muciniphila was shown in an in vitro intestinal model and upon addition of mucus, A. muciniphila abundance showed over 10 000‐fold increase, the highest ever observed in this model (Van Herreweghen et al ., ).…”