Phase-variable bacteria simultaneously express multiple capsules.

Capsular polysaccharides (CPSs) protect bacteria from host and environmental factors. Many bacteria can express different CPSs and these CPSs are phase variable. For example, Bacteroides thetaiotaomicron (B. theta) is a prominent member of the human gut microbiome and expresses eight different capsular polysaccharides. Bacteria, including B. theta, have been shown to change their CPSs to adapt to various niches such as immune, bacteriophage, and antibiotic perturbations. However, there are limited tools to study CPSs and fundamental questions regarding phase variance, including if gut bacteria can express more than one capsule at the same time, remain unanswered. To better understand the roles of different CPSs, we generated a B. theta CPS1-specific antibody and a flow cytometry assay to detect CPS expression in individual bacteria in the gut microbiota. Using these novel tools, we report for the first time that bacteria can simultaneously express multiple CPSs. We also observed that nutrients such as glucose and salts had no effect on CPS expression. The ability to express multiple CPSs at the same time may provide bacteria with an adaptive advantage to thrive amid changing host and environmental conditions, especially in the intestine.

Immunomodulatory Roles of Polysaccharide Capsules in the Intestine.

The interplay between the immune system and the microbiota in the human intestine dictates states of health vs. disease. Polysaccharide capsules are critical elements of bacteria that protect bacteria against environmental and host factors, including the host immune system. This review summarizes the mechanisms by which polysaccharide capsules from commensal and pathogenic bacteria in the gut microbiota modulate the innate and adaptive immune systems in the intestine. A deeper understanding of the roles of polysaccharide capsules in microbiota-immune interactions will provide a basis to harness their therapeutic potential to advance human health.

Diet modulates colonic T cell responses by regulating the expression of a Bacteroides thetaiotaomicron antigen.

T cell responses to symbionts in the intestine drive tolerance or inflammation depending on the genetic background of the host. These symbionts in the gut sense the available nutrients and adapt their metabolic programs to use these nutrients efficiently. Here, we ask whether diet can alter the expression of a bacterial antigen to modulate adaptive immune responses. We generated a CD4+ T cell hybridoma, BθOM, specific for Bacteroides thetaiotaomicron (B. theta). Adoptively transferred transgenic T cells expressing the BθOM TCR proliferated in the colon, colon-draining lymph node, and spleen in B. theta-colonized healthy mice and differentiated into regulatory T cells (Tregs) and effector T cells (Teffs). Depletion of B. theta-specific Tregs resulted in colitis, showing that a single protein expressed by B. theta can drive differentiation of Tregs that self-regulate Teffs to prevent disease. We found that BθOM T cells recognized a peptide derived from a single B. theta protein, BT4295, whose expression is regulated by nutrients, with glucose being a strong catabolite repressor. Mice fed a high-glucose diet had a greatly reduced activation of BθOM T cells in the colon. These studies establish that the immune response to specific bacterial antigens can be modified by changes in the diet by altering antigen expression in the microbe.