Pasteurized Akkermansia muciniphila improves irritable bowel syndrome-like symptoms and related behavioral disorders in mice

Abstract

Gut – brain communications disorders in irritable bowel syndrome (IBS) are associated with intestinal microbiota composition, increased gut permeability, and psychosocial disturbances. Symptoms of IBS are difficult to medicate, and hence much research is being made into alternative approaches. This study assesses the potential of a treatment with pasteurized Akkermansia muciniphila for alleviating IBS-like symptoms in two mouse models of IBS with different etiologies. Two clinically relevant animal models were used to mimic IBS-like symptoms in C57BL6/J mice: the neonatal maternal separation (NMS) paradigm and the Citrobacter rodentium infection model. In both models, gut permeability, colonic sensitivity, fecal microbiota composition and colonic IL-22 expression were evaluated. The cognitive performance and emotional state of the animals were also assessed by several tests in the C. rodentium infection model. The neuromodulation ability of pasteurized A. muciniphila was assessed on primary neuronal cells from mice dorsal root ganglia using a ratiometric calcium imaging approach. The administration of pasteurized A. muciniphila significantly reduced colonic hypersensitivity in both IBS mouse models, accompanied by a reinforcement of the intestinal barrier function. Beneficial effects of pasteurized A. muciniphila treatment have also been observed on anxiety-like behavior and memory defects in the C. rodentium infection model. Finally, a neuroinhibitory effect exerted by pasteurized A. muciniphila was observed on neuronal cells stimulated with two algogenic substances such as capsaicin and inflammatory soup. Our findings demonstrate novel anti-hyperalgesic and neuroinhibitory properties of pasteurized A. muciniphila, which therefore may have beneficial effects in relieving pain and anxiety in subjects with IBS.

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice

“…While pasteurization inactivates microorganisms and their production of SCFAs, this process also increases accessibility to extracellular bacterial proteins which resist heat denaturation 42 . Amuc_1100 is an outer membrane protein specific to A. muciniphila which appear to remain stable at pasteurization temperature, and recapitulates the beneficial effect of live or pasteurized A. muciniphila in the context of metabolic disorders and colitis 38,42,[81][82][83][84] . Various studies have shown that purified Amuc_1100* is an efficient activator of the TLR-2 receptor 37,42,85 .…”

Live and Pasteurized Akkermansia muciniphila Mechanisms of Action and Its Potential Use as an Aid in the Treatment of Non-communicable Diseases

“…In one study in mouse models (C57BL6/J mice subjected to neonatal maternal separation and Citrobacter rodentinum infection), supplemented with pasteurised A. muciniphila was shown to reduce visceral hypersensitivity by affecting intestinal barrier function. In addition, a reduction in anxiety-like behaviour, as well as memory impairment and an effect on pain sensations, has been shown [38].…”

Insights into the Mechanisms of Action of Akkermansia muciniphila in the Treatment of Non-Communicable Diseases

“…In addition to the use of A. muciniphila in the treatment of IBD, the use of postbiotic supplementation (pasteurized A. muciniphila ) in irritable bowel syndrome (IBS)-like symptoms has recently received attention. Meynier et al [ 59 ] aimed to investigate the effects of pasteurized Akkermansia muciniphila on alleviating IBS-like symptoms and related behavioral disorders in mice. The researchers used two mouse models to mimic IBS symptoms: (i) a non-inflammatory model to induce colonic hypersensitivity (NMS), and (ii) a Citrobacter rodentium post-infectious IBS (PI-IBS) model.…”

“…Moreover, the study revealed improvement in anxiety-like behavior and memory defects and neuroinhibitory effects with reduced anxiety and enhanced cognitive function in the PI-IBS model treated with pasteurized A. muciniphila. Of interest, the treatment did not significantly alter the overall composition of the fecal microbiota, indicating that its beneficial effects might be due to direct interactions with the host rather than altering microbiota composition [ 59 ].…”