Interplay between intestinal macrophages and microbiota
Macrophages form a well-established cell-type of the innate immune
system that probe the host or invading microbes using pattern
recognition receptors and exhibit efficient phagocytic and bactericidal
activity [65]. Studies using germ-free or gnotobiotic mice models
reported the potential role of gut microbiota in modulating macrophage
phenotypes in the colon. Emerging studies have demonstrated the
functional association of macrophages and gut microbiota that might be
crucial to further understand and treat several diseases associated with
gut dysbiosis-induced leaky gut syndrome. Despite the association of
pro-inflammatory M1 and M2 macrophage phenotype in intestinal
inflammatory and repair conditions respectively [66], the role of
specific bacterial species on modulating macrophage phenotype is less
studied. For example, bacteria such as Enterococcus faecalispolarize colonic macrophages toward the proinflammatory M1 phenotype in
mice [67]. In addition, few studies have demonstrated an indirect
association of dysbiosis with M1 phenotypes. For example, antibiotics
induced dysbiosis with reduced Firmicutes and Bacteroidetes and
decreased faecal concentrations of short chain fatty acids (SCFAs) have
been associated with the accumulation of pro-inflammatory macrophages
[68]. In contrast, Clostridium butyricum directly induced
IL-10 production by intestinal macrophages in inflamed mucosa and
triggered polarisation of the macrophages into the anti-inflammatory
phenotype through the TLR-2/MyD88 pathway [69]. In addition,Bacteroides fragilis and Clostridia class, Fusobacterium
nucleatum induce M2 polarization [70]. Lactobacillus
intestinalis and Lactobacillus johnsonii drive macrophage to M2
phenotype and resolve mercury induced injury and intestinal permeability
in vitro [71]. Lactobacillus johnsonii alleviates colitis via
promoting M2 macrophages [72]. Mytilus coruscus reduced
pro-inflammatory cytokines from macrophages in vitro and increased the
abundance of some probiotics like Anaerotruncus, Lactobacillus,
Desulfovibrio, Alistipe, Odoribacter, and Enterorhabdus in the colon and
improved intestinal barrier integrity in vivo [73]. In another
study, microbiota were observed to drive macrophage polarization towards
the M2 phenotype and subsequently promote stem cell differentiation
[74]. Interestingly, an in vivo study demonstrated the depletion of
macrophages alters bacterial gut microbiota by promoting fungal
overgrowth [75]. In another study, gut microbiota was shown to drive
macrophage-dependent intestinal stem cell self-renewal mechanisms
[76]. Moreover, microbial metabolites also have been studied in
intestinal epithelial barrier repair via modulating macrophages. For
example, butyrate, docosahexaenoic acid and other SCFAs reduce
inflammation and help repair the intestinal barrier by driving M2
macrophage polarization [77] [78] [79]. In addition,
bacterial components such as LPS and flagellin are reported to modulate
and activate M2 macrophages represented by IL-3 and TGF-b signaling
[80]. Macrophages infected by F. nucleatum upregulate IDO
(Indoleamina 2,3-diossigenasi) on the cell surface, suggesting an
additional mechanism whereby F. nucleatum might trigger
macrophage-driven immunosuppression [81]. These studies suggest an
explicit association of macrophages and gut microbiota and a careful
modulation of microbiota composition might trigger a favorable
macrophage phenotype to treat different disease conditions. Therefore,
identifying the key mechanisms of gut microbiota and their products in
regulation of macrophage phenotypes in the intestine needs further
investigation for the development of an effective therapeutic approach
for treating gut leakage and its associated diseases.