Impact of Cyanocobalamin and Methylcobalamin on Inflammatory Bowel Disease and the Intestinal Microbiota Composition

Abstract

Patients with inflammatory bowel disease (IBD) are usually advised to supplement various types of vitamin B12, because vitamin B12 is generally absorbed in the colon. Thus, in the current study, the influence of cyanocobalamin (CNCBL) or methylcobalamin (MECBL) ingestion on IBD symptoms will be investigated. Then, whether and how the application of various cobalamins would modify the taxonomic and functional composition of the gut microbiome in mice will be examined carefully. Dextran-sulfate-sodium-induced IBD mice were treated with MECBL or CNCBL; disease activity index (DAI) scores and intestinal inflammatory conditions of mice were evaluated. Fecal samples were collected; microbiota composition was determined with a 16s rRNA analysis; functional profiles were predicted by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt); and short-chain fatty acids were measured. The consequence of higher relative abundances of Enterobacteriaceae and isomeric short-chain fatty acids by cobalamin treatment revealed that a high concentration of CNCBL but not MECBL supplementation obviously aggravated IBD. A microbial ecosystem rich in Escherichia/Shigella and low in Lactobacillus, Blautia, and Clostridium XVIII was observed in IBD mice after a high concentration of CNCBL supplementation. In cobalamin-dependent enzymes, CNCBL was more efficient in the adenosylcobalamin system than MECBL and vice versa in the MECBL system. The distinct effects of various cobalamins were associated with the distribution and efficiency of vitamin-B12-dependent riboswitches. CNCBL had a strong inhibitory effect on all riboswitches, especially on btuB and pocR riboswitches from Enterobacteriaceae. CNCBL aggravated IBD via enhancing the proportion of Enterobacteriaceae organisms through riboswitch and enzyme systems. The present study provides a critical reference for offering a suitable amount and type of cobalamin during a symbiotic condition.

Oral vitamin B12 supplement is delivered to the distal gut, altering the corrinoid profile and selectively depleting Bacteroides in C57BL/6 mice

“…Zhu et al show that cyanocobalamin supplementation during DSS administration had a negligible effect on colitis outcomes, including weight loss and colon length reduction. 30 Furthermore, cyanocobalamin supplementation during DSS did not have a significant effect on microbial alpha diversity, 30 similar to our findings. This is in contrast with work in other organ systems, which has shown that cyanocobalamin exhibits anti-inflammatory effects again acute and chronic inflammation in mice.…”

Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis

“…Remarkably, members of the gut microbiota have evolved to preferentially bind various bioactive forms of cobalamin. A recent study described cyanocobalamin binding more efficiently to vitamin B12 responsive riboswitches compared to more bioavailable methylcobalamin (16). Bacteria capable of utilizing unique energy sources, such as hostassociated luminal mucus, synthesize, and release vitamin B12, which subsequently can be utilized by neighboring microbial species, forming an intestinal symbiosis (41).…”

“…By contrast, Bressenot et al (15) noted reduced intestinal barrier function in vitamin B12 deficient rats. A third study found variations in the effects of acute cobalamin administration in a murine model of colitis based on its bioactive state: methylcobalamin having more antiinflammatory properties, whereas synthetic cyanocobalamin had a more pro-inflammatory effect (16).…”

The Dynamic Interplay between the Gut Microbiota and Autoimmune Diseases

“…Because patients with IBD are usually advised to take cobalamin, Zhu et al investigated the influence of cyanocobalamin (CNCBL) or methylcobalamin (MECBL) ingestion on DSS-induced IBD mice by 16S rRNA analysis in fecal samples. These authors found that a high concentration of CNCBL but not MECBL supplementation markedly aggravated IBD, with an increasing proportion of Escherichia / Shigella and a decreasing abundance of Lactobacillus , Blautia , and Clostridium XVIII [109]. This finding may provide a novel reference for treating IBD patients based on the microbiota in the clinic.…”