The microbiome and diverticulitis: a new target for medical therapy?
Diseases of the Colon ReCtum Volume 57: 4 (2014) microbes in the human gastrointestinal tract contain 10 to 10 genes, and the size of this genome is =100 times larger that the size of our own genome. the aggregate, multiorganismic, genetic code of those varied microorganisms is referred to as the "microbiome." Recent clinical advances, such as the apparent success of fecal transplantation for treatment of recurrent Clostridium difficile colitis, have harnessed the curiosity of the lay public toward a new awareness of human dependence on microbiological diversity. this renewed interest has unleashed a variety of investigations into this topic, ranging from the impact of vaginal microbiota on reproductive health to the role of gut microorganisms in the pathogenesis of morbid obesity and Crohn's disease. the pathogenesis of diverticular disease has commonly been thought to be a result of a low fiber diet, leading to increased luminal pressures, microperforation, and local sepsis. although inflammation appears to be the final common pathway for disease, it is clear to most clinicians that not all patients have evidence of microperforation when they are subjected to crosssectional imaging. a number of authors have proposed alternative presentations of diverticular disease, such as segmental colitis associated with diverticular disease or symptomatic uncomplicated diverticular disease. Both of these disease entities have low grade inflammation as an underlying characteristic. these observations converge with earlier findings, which suggested that patients with asymptomatic diverticulosis can be demonstrated to have lymphoid infiltrates in macroscopically diseasefree areas of colonic mucosa. in this issue of Diseases of the Colon Rectum, Daniels et al offer a hypothesis for the role that the microbial mammalian metabolic axis might have on the pathogenesis of diverticular disease. there is little published clinical evidence suggesting a direct link between microbiota and diverticular disease; however, the authors extrapolate from other known relationships. for example, Daniels et al explore findings of altered microbiota in the flora of patients with colon cancer, irritable bowel syndrome, and iBD. although the finding of altered microbiota in various disease states is intriguing, there is still ample debate as to whether these changes are causative of disease or simply a phenotype of the disease process itself. the authors spend a considerable amount of time discussing the relationship between altered microbiota and obesity. obesity is associated with a low grade inflammatory state, and the authors suggest that obesity is a major risk factor for diverticular disease. there is still some debate regarding this assertion, and in any case the results of some prospective trials suggest that visceral fat may be associated with the development of diverticulitis. if a relationship does exist, however, targeting the inflammation obesity diverticulitis pathway might be fruitful. Recent work suggests that alterations in microbiota may be causative of obesity rather than a result of obesity. this effect has been demonstrated in both mice and in humans. Germ free mice that lack microbiota have significantly less body weight than normal mice, even with increased caloric consumption. transplantation of microbiota from obese mice to germ free mice is enough to trigger the onset of obesity in germ free mice. obese humans who had fecal transplants from lean individuals can be demonstrated to have increases in peripheral and hepatic insulin sensitivity. Daniels et al also evaluate pharmacologic attempts at manipulating the human microbiota for the purpose of altering the pathogenesis of diverticulitis. a number of small trials have examined the efficacy of mesalamine like compounds in the management of diverticulitis. in all of these studies, the outcomes of interest were symptom severity and change in bowel habits. trespi et al demonstrated that patients treated with rifaximin, ampicillin/sulbactam, and mesalamine had decreased symptomatology and were less likely to experience a microhemorrhagic phenomenon. other authors have randomly assigned patients with at least 2 episodes of acute diverticulitis to rifaximin, a poorly absorbed antibiotic, versus a combination The Microbiome and Diverticulitis: A New Target for Medical Therapy?
Diseases of the colon and rectum