To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions.

Abstract

Vitamins are organic compounds that are essential to the health of an organism. Humans cannot synthesize vitamins but obtain vitamins through dietary intake. Cobalamin, or vitamin B12, refers to a group of corrinoid molecules that contains a corrin ring with a central cobalt molecule [1]. Cobalamin is a cofactor for the highly conserved enzymes methionine synthase (MetH) and methylmalonyl-CoA mutase (MCM), which function in amino acid synthesis and fatty- and amino acid breakdown, respectively, in both bacteria and mammals [1]; therefore, cobalamin plays a key role in homeostatic functions. Indeed, in humans, cobalamin deficiency can lead to decreased activity of MetH and MCM and result in megaloblastic anemia in addition to severe neurological symptoms. Besides its role as a cofactor for MetH and MCM, cobalamin is also used by many bacteria as a cofactor for additional processes, including metabolism and gene regulation. Cobalamin impacts host–microbe interactions by altering host and bacterial physiology at intestinal and extraintestinal sites. We discuss the current understanding of cobalamin in host–microbiota–pathogen interactions, highlighting recent investigations that deepen our appreciation of this molecule. How do mammals acquire cobalamin? Only a limited number of bacteria and archaea generate cobalamin de novo [1]. Moreover, plants and fungi do not require cobalamin; therefore, humans obtain cobalamin through consumption of animal products. During digestion, cobalamin is absorbed in the ileum. Although some colonic bacteria produce cobalamin, humans are not able to uptake cobalamin produced at this location, and thus, the small intestine is the sole site of absorption. The mammalian protein intrinsic factor (IF) is essential to bind and absorb cobalamin. IF is produced in the stomach and binds cobalamin in the small intestine, in which IF-bound cobalamin is subsequently absorbed into circulation [2] (Fig 1). Open in a separate window Fig 1 Cobalamin in the healthy human intestinal tract. Ingested food containing cobalamin enters the stomach. IF is produced in the stomach and binds cobalamin in the small intestine. There, cobalamin–IF complexes are absorbed by host enterocytes in the terminal ileum (indicated by outward arrows in small intestine). In the colon, the microbiota take up unabsorbed cobalamin. Additionally, some members of the microbiota produce cobalamin, which can also be taken up by other microbiota members. Cobalamin that remains unabsorbed by the host and not taken up by the microbiota is excreted in stool (outward arrow in colon). IF, intrinsic factor.