Data from a first proof-of-concept study in human volunteers indicated that direct instilling A. muciniphila into the colon of healthy adults led to rapid changes in gene expression in the colonic mucosa.
The paper, which was published in Cells, also details a study with mice that showed that Akkermansia may reduce inflammation in the abdominal lining (peritonitis) and mortality via a mechanism that is linked to Myd88, a central adaptor molecule for most toll-like receptors, proteins that play a key role in the immune system. This deepens our understanding of the mechanism of action of this bacterium and its impact on intestinal wound healing.
“This study illustrates how understanding the complex interactions between host and a specific potential beneficial microbe may support the development of future therapeutic strategies targeting the gut microbiota,” wrote scientists from Belgium, The Netherlands, Sweden, and Finland.
Akkermansia muciniphila has attracted growing interest for its health-promoting effects. In rodents, treatment with A. muciniphila reduces obesity and related disorders, such as glucose intolerance, insulin resistance and gut permeability.
The species Akkermansia muciniphila reportedly has an abundance of about 3% in the human colon, and its abundance in the intestinal mucus layer is inversely correlated with BMI, type 1 diabetes, and bowel disease in humans. Akkermansia is known to produce nutrients that feed intestinal cells responsible for producing the intestinal mucus layer, helping to maintain healthy intestinal barrier function, control gut permeability, and control low grade inflammation in the gut.
Much of the research into the species has been conducted in Belgium at the Catholic University of Louvain, and a spin-off company called A-Mansia was launched several years ago focusing on commercial development of A. muciniphila products.
The researchers behind the new study, and others, have previously reported that A. muciniphila activates different Toll-like receptor and modulates the immune system, but it was not clear if its beneficial effects on wound healing were linked specifically to MyD88.
To shine light on this issue, Radu Bachmann and his co-workers investigated the effects of treating lab mice with A. muciniphila MucT for two weeks prior to surgically perforating their colon to induce peritonitis. The researchers also conducted the experiment in mice genetically engineered to not express MyD88.
The results showed that, a week after surgical perforation, the Akkermansia-treated animals had significantly less severe peritonitis and lower mortality, compared to non-treated animals. The Akkermansia-treated mice were also found to have better wound healing, and higher production of IL22, consistent with other studies.
However, in the MyD88 knockout mice, no such benefits were observed.
Dr Bachmann and the team also performed a proof-of-concept pilot study which exposed healthy humans to A. muciniphila for two hours. Colonic biopsies were taken before and after Akkermansia exposure.
This experiment showed that there were increased levels of A. muciniphila at the mucus level two hours after instillation, and that this was associated with significant changes in the expression of genes involved in “the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa”.
The researchers wrote: “Our data suggest that A. muciniphila is safe and can rapidly induce changes in the expression of genes in the colonic mucosa exposed to A. muciniphila.
“However, the question remains if we can extrapolate these in vivo animal findings to humans, and additional experiments in humans are therefore inevitable,” concluded the researchers.
2022, 11(17), 2666; doi: 10.3390/cells11172666
“Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism”
Authors: R. Bachmann et al.