There was collusion: Microbes in inflammatory bowel disease.

摘要: Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory diseases that affect the gastrointestinal tract and includes ulcerative colitis (UC) Crohn’s (CD). UC is restricted mucosa colon, whereas lesions in CD are often discontinuous, occur across entire wall organ (transmural), involve any part from mouth anus. Infectious etiologies have been investigated since was first described 1932. In their seminal paper, Oppenheimer, Ginzberg, Crohn describe detail culture conditions they used demonstrate neither intestinal tuberculosis nor caused by bacterial pathogens [1]. Over years, search for infectious causes IBD has continued even dabbled controversy. 1993, before his foray into antivaccine movement with studies claiming an association between measles, mumps, rubella (MMR) vaccine autism, gastroenterologist Andrew Wakefield published measles virus particles could be found tissue specimens patients [2]. The results were never reproduced [3]. On other hand, early life antibiotic usage associated IBD, somewhat paradoxically, antibiotics sometimes as adjunctive treatment implicating bacteria [4]. It now over 80 years described, role microbes remains unclear. While single causative agent remained elusive, origin may explained aberrant response community reside gut, microbiota. Other excellent reviews articulated how shifts communities subsequently sustain IBD. However, this microbiota does not preclude possibility specific agents contribute key members disproportionate effect akin pathogen, nonbacterial received sufficient consideration. pearl, we review myriad interrogated laboratory models roles pathogenesis, highlighting central importance understanding host–microbe interactions. Infectious triggers The existence pathogen trigger intriguing because pathology similar which occurs during infection Mycobacterium, Yersinia, Salmonella, Shigella, Campylobacter species [5]. For instance, share predilection terminal ileum presence granulomas histopathology, Mycobacterium avium paratuberculosis (MAP) Johne’s ruminants, bears striking resemblance CD. Multiple groups tested thousands samples MAP without reaching definitive conclusion [6]. Rather than directly initiating responsible exacerbating or sustaining disease. Clostridium difficile colonization cytomegalovirus (CMV) reactivation flares, though likely consequence inflammation medications. addition classical pathogens, commensal organisms disease-causing potential, referred pathobionts, attention, including Bacteroides fragilis, Helicobacter hepaticus, Enterococcus faecalis. particular, adherent-invasive Escherichia coli (AIEC) isolated ileal attention [7]. AIEC Enterobacteriaceae utilize electron acceptors such nitrate byproducts host response, can aggravate cause manifestations, colorectal cancer [8, 9]. Targeting respiratory pathways pathobionts reasonable intervention strategy [10]. The incapacitate protective mechanisms, thereby lowering threshold subsequent (Fig 1). Episodes acute gastroenteritis, most commonly Salmonella Campylobacter, precede onset some [11]. Interestingly, recurrent cycles resolution mice lead via loss mechanism lipopolysaccharide detoxification [12]. Also, protozoan Toxoplasma gondii leads break immune tolerance toward inducing differentiation microbiota-reactive T cells [13]. Thus, while appear transmissible, play active IBD. Open separate window Fig 1 Model pathogenesis. Variable changes microbiome, whether agent, emergence pathobiont, commensals, individual who susceptible genetic risk alleles environmental factors, diet lifestyle smoking. These episodes responses enteric (blue spikes) time eventually immobilize mechanisms (orange line) declines point crossing symptomatic clinical (dashed red line), resulting