Microbial colonization influences gut homeostasis and immunocyte activity. In Nature Medicine, Matzinger and colleagues report a tripartite 'conversation' among commensal microbes, B cells and gut epithelium that profoundly affects host metabolic function. Mice that lack B cells or secretory immunoglobulins have less absorption and use of lipids. Gene-expression profiling shows higher expression of interferon-inducible genes and lower expression of those encoding molecules involved in fat metabolism, especially those regulated by the transcription factor GATA-4. Network analyses show that the interferon-inducible GTPase GBP6 connects these differently regulated gene subsets. Intriguingly, upregulation of the cytosolic DNA sensor ZBP1 (DAI) is likewise upregulated in gut epithelial cells in mice that lack B cells. Thus, gut tissues increase interferon-related responses to compensate for the lack of secretory immunoglobulins A and M, but this response leads to diminished functioning of metabolic pathways.

Nat. Med. (20 November 2011) doi:10.1038/nm.2505