Gut microbiota and atherosclerosis: role of B cell for atherosclerosis focusing on the gut-immune-B2 cell axis

Abstract

Atherosclerosis is the leading cause of cardiovascular mortality and morbidity worldwide and is described as a complex disease involving several different cell types and their molecular products. Recent studies have revealed that atherosclerosis arises from a systemic inflammatory process, including the accumulation and activities of various immune cells. However, the immune system is a complicated network made up of many cell types, hundreds of bioactive cytokines, and millions of different antigens, making it challenging to readily define the associated mechanism of atherosclerosis. Nevertheless, we previously reported a potential persistent inflammatory process underlying atherosclerosis development, centered on a pathological humoral immune response between commensal microbes and activated subpopulations of substantial B cells in the vicinity of the arterial adventitia. Accumulating evidence has indicated the importance of gut microbiota in atherosclerosis development. Commensal microbiota are considered important regulators of immunity and metabolism and also to be possible antigenic sources for atherosclerosis development. However, the interplay between gut microbiota and metabolism with regard to the modulation of atherosclerosis-associated immune responses remains poorly understood. Here, we review the mechanisms by which the gut microbiota may influence atherogenesis, with particular focus on humoral immunity and B cells, especially the gut-immune-B2 cell axis.

NEIL3-deficiency increases gut permeability and contributes to a pro-atherogenic metabolic phenotype

“…7 . We hypothesize that a similar pathogenic interplay may occur in humans, as alterations in gut microbiota have been implicated in atherogenesis also in the human setting 48 . We have previously demonstrated an association between a polymorphism in NEIL3 and increased risk of myocardial infarction 7 , as well as increased expression of NEIL3 in human atherosclerotic plaques 8 , supporting a role for NEIL3 in human atherogenesis.…”

The Types and Proportions of Commensal Microbiota Have a Predictive Value in Coronary Heart Disease

“…Although some studies investigating the relationship between commensal microbiota and CHD have been conducted previously [ 6 ], our synthetic analysis is the first to investigate the types of commensal microbiota that are commonly associated with CHD. Moreover, our findings revealed several specific types of commensal microbiota that commonly exist or coexist in the atherosclerotic plaque, blood, or feces of patients with CHD.…”

“…Additionally, to observe the progression of the disease, there is an increasingly important clinical value in discovering a predictive biomarker for CHD. Although the molecular mechanisms responsible for the development of CHD are not completely understood, recent studies have highlighted the critical role of commensal microbiota in CHD [ 4 , 5 , 6 ], with alterations in the gut microbiota being linked to CHD progression [ 4 ]. However, a synthetic analysis of the predictive value of specific types of commensal microbes in CHD patients has not yet been performed.…”

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

“…33 Differ from the pro-atherogenic effects of macrophages and specific T cells subsets, B cells may exert a more complex effect in the development of atherosclerotic plaque through antibody production, which is not yet fully explored. 34 As mentioned above, the role of immune cell responses is central in the progression of atherosclerotic plaque. An anti-inflammatory therapy with canakinumab, a monoclonal antibody targeting IL-1β, was conducted randomly, involving 10,061 patients with previous myocardial infarction.…”