Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis

Abstract

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.

Trimethylamine N-Oxide, a Gut Microbiota-Derived Metabolite, Is Associated with Cardiovascular Risk in Psoriasis: A Cross-Sectional Pilot Study

“…Recent studies suggest that alteration in gut microbiome composition is another factor that may influence formation and progression of atherosclerotic plaque [32]. Moreover, gut dysbiosis has also been linked to psoriasis and its comorbidities [33].…”

Role of gut microbiota in the immunopathology of atherosclerosis: Focus on immune cells

“…The gut microbiota‐derived metabolite, TMAO has been suggested as a marker and mediator of cardiovascular diseases in recent years, and its precursor, TMA was proposed to be toxic several decades ago 42 . Conversely, GM‐derived SCFAs enhance gut barrier and reduce systemic inflammation, playing an athero‐protective role 42 . Other metabolites, such as secondary BAs produced by the host and modified by GM, also modulate the immune response of atherosclerosis 43 …”

The Microbiome and Its Implications in Cancer Immunotherapy

“…There are a limited number of research studies regarding the communication between gut microbiota and the mTOR pathway, that elucidate mTOR signaling in microbiota-associated metabolic and immune regulations [ 243 ]. Gut microbiome also plays a significant role in the immune system in controlling the functionality and development of gut-associated lymphoid tissues (GALT), including mesenteric lymph nodes, isolated lymphoid follicles, and Peyer’s patches [ 244 , 245 ]. Apart from this gut microbiome secreted products are very important for the immune system to differentiate self from nonself (invaders) at very young stage and activation and maintenance of innate hematolymphoid cells (ILC1, 2, and 3), cytotoxic and noncytotoxic and helper lymphoid cells and natural killer (NK) cells [ 246 ].…”