Microbial Translocation Disorders: Assigning an Etiology to Idiopathic Illnesses

Abstract

Gut microbes are immunologically tolerated in the gastrointestinal tract but trigger aggressive immune responses upon translocation across the gut barrier. Although oral tolerance, a physiological process that dampens immune responses to food proteins and commensal microbiota, remains poorly defined, significant progress was made during and after the Human Immunodeficiency Virus epidemic in the 1980s and the discovery of regulatory T cells in 1995. Additional insight was gained after the discoveries of innate lymphoid cells in 2008 and the functional elucidation of mucosal mast cells. Prior to the historical discovery of human pathogens, the etiologies of most human diseases were considered unknown. The same was true about many genetic disorders prior to the Human Genome Project. Here, we hypothesize that many of the remaining idiopathic conditions, including autoimmune, fibroproliferative, and neuropsychiatric diseases as well as some cancers, can be considered microbial translocation disorders triggered by the host immune responses to extraintestinal gut microbes and/or their constituent parts. In addition to microbial translocation, we also discuss potential interventions for intestinal barrier rehabilitation, including antibodies against tumor necrosis factor-like ligand 1A and membrane lipid replacement supplements.

The Role of Lactylation in Mental Illness: Emphasis on Microglia

“…In our previous work, we have discussed microbial translocation from the GI tract into the host systemic circulation, suggesting that the pathogenesis of several idiopathic diseases could be explained by the immune responses to extraintestinal microbial proteins [193]. As higher gut and BBB permeability markers, including the soluble form of CD14 (sCD14), were documented in neuropsychiatric illness, this pathology may, at least in part, result from microbial migration through the gut barrier [194][195][196].…”