Which species are in your feces?

Abstract

Nosocomial infections (i.e., infections acquired as a result of treatment in a hospital or health care unit) result in approximately 100,000 deaths and cost more than 25 billion dollars per year in the US alone. These infections are caused primarily by bacteria and affect mainly immunosuppressed patients. However, not all patients acquire infections, and the events leading up to infection are unclear. In this issue of the JCI, Ubeda et al. report how acquisition of one such infection, vancomycin-resistant Enterococcus faecium (VRE), is linked to a shift in the microbial flora following antibiotic treatment. This study highlights the potential for high-throughput sequencing of intestinal microbiota as a means to identify high-risk populations.

Figure 1. Antibiotic treatment leads to long-term changes in the commensal flora and susceptibility to VRE.

(A) In the steady state, interactions between commensal bacteria and host cells in the intestine — primarily epithelial cells — result in the production of antimicrobial effector proteins (AMPs), such as REGIIIγ and RELMβ, that shape the commensal populations. The production of AMPs in this context may be dependent on NF-κB, which is presumed to be activated by TLR recognition of commensal bacterial products. In this state, mice are resistant to VRE infection. (B and C) Following transient antibiotic treatment, the numbers and diversity of the bacterial populations are severely reduced. Antibiotic treatment — presumably through a reduction in commensal bacteria — also results in decreased expression of AMPs. These changes result in long-lived increased susceptibility to VRE.

Figure 2. The role of the immune system in regulation of the commensal microflora.

(A) In healthy subjects, recovery from antibiotic treatment results in minor changes to the diversity of the commensal flora. Immune mechanisms, including production of commensal-specific IgA, effector and regulatory cytokines, and retinoic acid that can act on IECs and other immune cells, may all contribute to the maintenance of intestinal homeostasis. (B) In contrast, immunocompromised patients that have impaired B cell, T cell, and DC responses often do not recover bacterial diversity following antibiotic treatment; in some cases, a single genus dominates the flora.