Mechanisms and Applications of Bacterial Sporulation and Germination in the Intestine

Abstract

Recent studies have suggested a major role for endospore forming bacteria within the gut microbiota, not only as pathogens but also as commensal and beneficial members contributing to gut homeostasis. In this review the sporulation processes, spore properties, and germination processes will be explained within the scope of the human gut. Within the gut, spore-forming bacteria are known to interact with the host's immune system, both in vegetative cell and spore form. Together with the resistant nature of the spore, these characteristics offer potential for spores' use as delivery vehicles for therapeutics. In the last part of the review, the therapeutic potential of spores as probiotics, vaccine vehicles, and drug delivery systems will be discussed.

Keywords: drug delivery system; inflammatory bowel disease; microbiome; probiotics; spore; sporobiota; vaccine vehicle.

Figure 1

Interactions between spore forming bacteria and the intestine. Spore forming bacteria can act in the intestine both as spore and vegetative cells after germinating under the influence of germinants such as bile acids, amino acids, and other compounds. On the left, interactions with pathogenic spore forming bacteria are illustrated. Once sporulated, these bacteria produce toxins that act locally by interacting with the epithelium and altering immune responses, leading to cell death, tissue damage, and subsequently reduced epithelial barrier function causing a leaky gut. When this happens, inflammatory responses are evoked, and certain bacteria and toxins can travel from the gut to the bloodstream leading to damage in other places in the body such as motor nerve endings which ultimately leads to paralysis. On the right, interactions with beneficial spore forming bacteria are illustrated. Spores can induce GALT development and maturation and proliferation of T and B cells. Mature B cells produce IgA which benefits the epithelial barrier function and promotes bacterial tolerance. This epithelial barrier function is also improved by the action of SCFA, produced by vegetative commensals which are often spore formers. In addition, SCFA are linked to improved gut homeostasis and suppressed inflammatory responses.