Figure 3. Model of metabolic relationships in the gastrointestinal tract.

The gut serves as a direct interface with the outside world and the foods we consume. A single epithelial cell layer separates the contents of the intestinal lumen from the lamina propria where DCs, macrophages, ILCs, and T cells reside. Peyer’s patches are interspersed along the epithelium, which in addition to supporting sampling of luminal antigens by DCs and M cells, house germinal centers that maturate IgA-secreting B cells with Tfh cell help. B cells augment glycolysis upon activation and depend on pyruvate import via Mpc2 for longevity as long-lived plasma cells (LLPCs). Plasma cell hunger for glucose may restrict this nutrient from Tfh cells, however Tfh cells downregulate glycolysis in response to expression of their lineage defining transcription factor Bcl6. In addition, GCs contain areas of hypoxia that impinge on B cell function like class switch recombination (CSR). Commensal bacteria produce metabolites such as short chain fatty acids (SCFAs) from the fermentation of dietary fiber, which influence B cell metabolism and promote IgA secretion. The presence of SCFAs and vitamins support maintenance of barrier function by promoting the development and survival of Tregs and ILCs, respectively. Homeostatic signals secreted by gut resident immune cells (e.g. IL-10) may also modulate metabolism and therefore control their activation state.