The gut microbiota and irritable bowel syndrome: friend or foe?

Abstract

Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS), once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gut microbiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall, and maintenance of homeostasis in the gastrointestinal tract. A subset of patients with IBS may have a quantitative increase in bacteria in the small bowel (small intestinal bacterial overgrowth). Qualitative changes in gut microbiota have also been associated with IBS. Targeting the gut microbiota using probiotics and antibiotics has emerged as a potentially effective approach to the treatment of this, hitherto enigmatic, functional bowel disorder. The gut microbiota in health, quantitative and qualitative microbiota changes, and therapeutic manipulations targeting the microbiota in patients with IBS are reviewed in this paper.

Figure 1

(1) Commensal bacteria (2) Pathogenic bacteria (3) Mucus layer (4) Intestinal epithelium (5) Peyer's patch (6) Tight junction protein (7) Paneth cell (8) Toll-like receptors (9) Dendritic cell (10) T cell (11) Degranulation of mast cells (12) Small intestinal bacterial overgrowth. The intestinal microbes may form a natural barrier to pathogenic bacteria. Therefore, any qualitative or quantitative change in the gut microbiota leads to the instability of the gut microbial ecosystem. It facilitates the entry of pathogenic bacteria and allows them to adhere to the wall of the intestinal epithelial cell. Degranulation of mast cells releases substances that increase the permeability of mucosa resulting in a reduction in the integrity of the tight junctional protein complex. Luminal bacteria or bacterial products such as peptidoglycans and lipopolysaccharides interact with Toll-like receptors on dendritic cells and macrophages. After processing, these cells present the antigen to T cells leading to the production of cytokines, chemokines which cause inflammation in the gastrointestinal tract. Paneth cells are found throughout the small intestine and secrete alpha defensins and lysozyme which, not only eliminate pathogenic bacteria, but also maintain the integrity of the intestinal membrane. Lymphocytes are found in a more organized structure called lymphoid follicles. M cells play an important role in transporting bacteria and microbial particles from the lumen to the lymphoid follicles. The areas around M cells, called Peyer's patches, facilitate the mucosal immune response.