Intestinal Fibrosis and Gut Microbiota: Clues From Other Organs

Abstract

Fibrosis is a complex and difficult to elucidate pathological process with no available therapies. Growing evidence implicates intestinal microbiota in the occurrence and development of fibrosis, and the potential mechanisms involved in different organs have been explored in several studies. In this review, we summarize the causative and preventive effects of gut microbiota on intestinal fibrosis, as well as the relationships between gut microbiota and fibrosis in other organs. Interestingly, several colonized microbes are associated with fibrosis via their structural components and metabolic products. They may also play essential roles in regulating inflammation and fibroblast activation or differentiation, which modulates extracellular matrix formation. While the relationships between intestinal fibrosis and gut microbiota remain unclear, lessons can be drawn from the effects of gut microbiota on hepatic, cardiac, nephritic, and pulmonary fibrosis. Various intestinal microbes alterations have been detected in different fibrotic organs; however, the results were heterogeneous. Mechanisms by which the intestinal microbiota regulate fibrotic processes in other organs, such as novel metabolic products or specific microbes, are also discussed. The specific microbiota associated with fibrosis in other organs could instruct future studies aiming to discover prospective mechanisms regulating intestinal fibrosis.

The breast tissue microbiome, stroma, immune cells and breast cancer

“…Percentage fibrosis in breast tissue was associated with microbial community differences with a positive correlation with the phyla Spirochaetes and genera Spirochaeta and Actinobacteria Adlercreutzia and an inverse correlation with the phyla Firmicutes and with the genera Clostridium and Staphylococcus . While no data exists on histologic assessment of breast tissue fibrosis in association with the tissue microbiome, gut microbiome studies have demonstrated microbiome associations with tissue fibrosis in the liver, heart, kidney, lung and intestine with variations in bacterial effects by anatomic site [34] . For example, one study reported a decrease in the relative abundance of Actinobacteria in the gut microbiome of patients with pulmonary fibrosis and others showed tissue-specific associations with increased or decreased relative abundance of various members of the phyla Firmicutes in association with fibrosis of various organs [ 34 , 35 ].…”

“…While no data exists on histologic assessment of breast tissue fibrosis in association with the tissue microbiome, gut microbiome studies have demonstrated microbiome associations with tissue fibrosis in the liver, heart, kidney, lung and intestine with variations in bacterial effects by anatomic site [34] . For example, one study reported a decrease in the relative abundance of Actinobacteria in the gut microbiome of patients with pulmonary fibrosis and others showed tissue-specific associations with increased or decreased relative abundance of various members of the phyla Firmicutes in association with fibrosis of various organs [ 34 , 35 ]. Another study evaluated the gut microbiome with 16S sequencing of V1-V2 in healthy post-menopausal women undergoing negative screening mammography [36] .…”

Current Topics of the Mechanism of Intestinal Fibrosis in Crohn’s Disease

“…Recent animal studies have demonstrated that these immune system cells response to specific bacteria and bacterial cell components (peptide glycans) in the intestinal tract can result in the secretion of cytokines and growth factors such as TGF-β1 and CTGF, and the activation of myofibroblasts. It is also reported that the sustained activation of ECM-producing cells worsens intestinal fibrosis [18,29,40]. Bacteria such as Mucispirillum schaedleri and Ruminococcus in the cecum and Streptococcus and Lactobacillus in the ileum were positively correlated with fibrosis in the tumor necrosis factor-like cytokine 1A (TL1A) transgenic mouse model [42].…”

“…In addition to the paracrine signals from immune and non-immune cells described above, myofibroblasts are activated by a variety of mechanisms, including autocrine factors secreted by myofibroblasts and pathogen-associated molecular patterns (PAMPs) of microbial origin that interact with pattern recognition receptors such as Toll-like receptors (TLRs) [18,40]. Toll-like receptors, consisting of TLR1 to TLR9, serve as sensors of the gut microbiota and are important in maintaining intestinal homeostasis, regulating immune responses and the formation of bacterial flora [41].…”

“…Toll-like receptors, consisting of TLR1 to TLR9, serve as sensors of the gut microbiota and are important in maintaining intestinal homeostasis, regulating immune responses and the formation of bacterial flora [41]. In particular, TLR4 signaling promotes pro-fibrotic activation of intestinal fibroblasts, enhances NF-κB promoter activity and increases collagen contraction [30,40].…”