9 WORLD GASTROENTEROLOGY NEWS JULY 2014 Editorial | Expert Point of View | WDHD News | WGO & WGOF News | WGO Global Guidelines | Calendar of Events were always present in all samples from the same individual. Dysbiosis as a cause of disease An imbalance of the normal gut microbiota composition is called dysbiosis. Different diseases have been associated with changes in the compo-sition of the gut microbiota. The world is facing a global health crisis provoked by an obesity epi-demic. The incidence of malignant forms of obesity that are associated with cardiovascular complications, the metabolic syndrome, is steadily increasing in Western countries. Some recent data on the metabolic syn-drome suggest that changes in gut mi-crobiome composition may play a role in the disorder. Studies performed in mice revealed a shift in the abundance of Bacteroidetes and Firmicutes11. In addition, recent human studies have shown that low genetic diversity in the gut microbiome increases the risk of several features associated with the metabolic disorders12. The study recruited obese and non-obese indi-viduals and those with a low bacterial gene count showed an inflammatory profile (increased C-reactive pro-tein), disturbed glucose homeostasis (hyperglycemia, insulin resistance) as well as body fat accumulation (leptin resistance). Surprisingly, those altera-tions were linked to reduced microbial diversity independently of the pres-ence of obesity or not. A subsequent study13 revealed that a low-caloric diet including prebiotics (5-6g of inulin per day) increases the diversity of the intestinal microbiota, and reduces inflammatory abnormalities. In animal models, transplantation of gut microbiota from obese mice to non-obese, germ-free mice resulted in transfer of metabolic syndrome-associated features from the donor to the recipient14. The mechanisms advocated are the provision of ad-ditional energy by the conversion of dietary fiber to short-chain fatty acids, effects on gut-hormone production, and increased intestinal permeability causing elevated systemic levels of lipopolysaccharides. The contact with these antigens seems to contribute to low-grade inflammation, a character-istic trait of obesity and the metabolic syndrome. Presumably, obesity affects the diversity of the gut microbiota and probably, the way individuals harvest energy from nutrients. The possible role of the intestinal metabolome on the development of cardiovascular risk is another hot is-sue. Phosphatidylcholine is a phos-pholipid involved in several metabolic functions, including the synthesis of neurotransmitters and amino acids, or structural features, such as being part of the cell membrane. Recent studies show that some members of the gut microbiota can degrade phosphati-dylcholine to toxic metabolites, in particular to trimethylamine N-oxide (TMAO)15, whose plasma levels are directly related to risk of cardio-vascular events. In human studies, administration of a course of broad spectrum antibiotics decreases TMAO levels, demonstrating the contribu-tion of some gut microbes to plasma TMAO. These findings reinforce the concept the microbiota is a metabolic organ that in addition to beneficial effects may also be involved in certain pathophysiological mechanisms. One of the major hypotheses un-derlying the pathogenesis of inflam-matory bowel disease (IBD) is the presence of abnormal communica-tion between gut microbial com-munities and the mucosal immune system16. Luminal bacteria appear to provide the stimulus for immune-inflammatory responses leading to mucosal injury. There is also some evidence showing that the microbiota of patients with IBD differs from that of healthy subjects. Differences include low biodiversity of dominant bacteria, high variability over time, and changes both in composition and spatial distribution (high concentra-tions of mucosa-adherent bacteria). The microbiota of Crohn’s disease pa-tients is characterized by a decrease in Faecalibacterium prausnitzii17 as well as increased numbers of the Proteo-bacteria and Actinobacteria phyla18. Some other associations of human conditions with particular microbiota characteristics have been described such as irritable bowel syndrome, psoriasis, colorectal carcinoma and childhood-onset asthma, but consis-tency among studies is still poor. Irritable bowel syndrome (IBS) is another chronic digestive disorder. Although no structural abnormalities have been demonstrated, molecular changes such as increased permeability of the intestinal barrier and increased visceral sensitivity are common features in IBS sufferers. Some evidence sug-gests that gut microbes can be involved in the origin of such alterations. Recent data suggest decreased diversity in small-bowel microbiota of patients with IBS, with increased abundance of gram-negative organisms19. Microbial therapeutics Even if associations of dysbiosis with disease do not necessarily predict cause-effect relationships, there is growing interest to develop strategies that will improve the ‘physiological’ quality of the human gut microbial ecosystem for health benefits. As suggested by experts, the future of a healthy human gut microbiota may include the restoration of our ances-tral microbial ecology. According Cho and Blaser20 there are two possible types of restoration. The first involves restoring ancient organisms in healthy hosts that lack them, as prophylaxis against future risk of disease. The second type of restoration could be therapeutic, when the etiological extinctions or imbalances are clearly identified. This scientific boundary will require an understanding of the
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