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Sepsis constitutes a global burden on medical care and accounts for nearly 20% of reported global mortality.1 The development of sepsis is complex, though the triggering of a disproportional systemic proinflammatory response is considered pivotal in driving organ dysfunction and subsequent mortality. As functional pattern recognition receptors, toll-like receptors (TLRs) play a predominant role in this context. Hence, approaches aimed at limiting their activation are considered valuable strategies for mitigating the organ damage and mortality occurring during the advancement of sepsis. The gut microbiota’s central importance in human health and its influence on sepsis progression, prompted a closer examination of specific bacterial strains.2 Akkermansia muciniphila (Akkermansia) holds particular potential as a next-generation beneficial bacteria in this context as we and others showed promising effects of this bacterium in preventing the progression of various pathological conditions linked to disruptions in immune system regulation and metabolic imbalances (ie, type 2 diabetes, obesity, hepatic steatosis, cancer therapies) (for review3). Akkermansia has the capability to stimulate appropriate immune responses and produces biologically active compounds that can influence the functioning of nearly every system in the body. We recently discovered that live Akkermansia protects against anastomotic leakage-induced peritonitis/sepsis and mortality by improving wound healing during colonic wall defect through mechanisms possibly involving interleukin (IL)-22 signalling and requiring TLR signalling through myeloid differentiation primary response 88 (MyD88) in the intestinal cells (figure 1).4 Among the suggested mechanisms, it was previously shown that Akkermansia produces several active compounds such as specific proteins (eg, Amuc_1100, P9), bioactive lipids (eg, diacyl phosphatidylethanolamine) or …
Contributors All authors contributed equally to the discussion, writing, correction and drawing of the figure.
Competing interests PDC is inventor on patent applications dealing with the use of specific bacteria and components in the treatment of different diseases. PDC was cofounder of The Akkermansia Company SA and Enterosys S.A.
Provenance and peer review Commissioned; internally peer reviewed.