Dangerous Disappearing Act: Commensal Gut Microbiota After Acute Severe Insults

Abstract

The trillions of cells that make up the human gut micro-biota are a double-edged sword, often protecting the hostfrom serious infection, but capable of causing lethalinflammation and overwhelming sepsis. This Janus-facedcharacteristic of the gut microbiota resembles the immunesystem itself, a powerful defense that can turn on its host.Altered gut microflora is involved in the pathogenesis of awide variety of diseases, including metabolic syndrome,obesity, congestive heart failure, pancreatitis, inflammatorybowel disease, and critical illness [1–4]. As Hayakawaet al. point out in this issue of Digestive Diseases andSciences, the gut microbiota is also dramatically changedin acute trauma, out-of-hospital cardiac arrest, and cere-brovascular disease [5]. These authors document the sud-den disappearance of commensal bacteria after acutesevere insults, raising the question, why?Most studies of gut microbiota in critical illness haveexamined hospitalized patients receiving intensive care[4, 6]. Shimizu et al. have shown that the gut microbiota issignificantly altered in patients with systemic inflammatoryresponse syndrome (SIRS) [4, 6]. Until now, the timing ofchanges in gut ecology has been unknown. In this study,Hayakawa et al. followed 15 acutely critically ill patientsfrom their initial presentation to the emergency departmentthrough 2 weeks of hospital care and made three novelobservations [5]. Compared to healthy controls, patientswith acute trauma/critical illness had an immediate thou-sand-fold reduction in the numbers of commensal gutbacteria. Obligate anaerobes were most affected by thesudden destruction of gut flora. Overgrowth of entericpathogens occurred over the following 2 weeks of hospi-talization, while commensal bacteria did not recover.The cause of altered gut microbiota among hospitalizedpatients has been variously ascribed to antibiotic treatment,inadequatenutrition,andotherstressors[7].Itiswellknown,for instance, that the obliteration of anaerobic gut flora withbroad-spectrum antibiotics predisposes to colonization andovergrowth by Clostridium difficile [8]. Hayakawa et al.showed here that anaerobes and Lactobacillus disappearsuddenly and in the early phase of illness. Fecal swabs takenin the emergency room within 6 h of a patient’s arrivalshowed the destruction of commensal bacteria before anti-biotic treatment, suggesting that the mechanism of imme-diate microbial loss does not involve antibiotics.Observational studies suggest a link between the pres-ervation of gut microbiota and survival during critical ill-ness [4]. Shimizu et al. reported that gut flora depletion,and loss of obligate anaerobes in particular, increases therisk of gut-derived sepsis, enteritis, and mortality [4, 9].Changed gut flora and impaired intestinal barrier functionare thought to promote the movement of endotoxin and gutbacteria into the portal circulation and gut lymphatics [7].These events exacerbate system inflammatory damage inhospitalized patients, leading to multi-organ dysfunctionsyndrome and death [7].The bacteria that are destroyed during acute severe stress,obligate anaerobes and Lactobacillus, have been shown toprotect the host from infection by competitive exclusion ofpathogens, production of antimicrobial substances, andprevention of pathogen adhesion to epithelial cells [10].