Folate and vitamin B12 deficiency exacerbate inflammation during Mycobacterium avium paratuberculosis (MAP) infection

Publication Date: 4 January 2023

Vaccaro, J.A. et al. (2023) Folate and Vitamin B12 Deficiency Exacerbate Inflammation during Mycobacterium avium paratuberculosis (MAP) Infection. Nutrients 15, 251. DOI: 10.3390/nu15020261

Crohn’s disease (CD) is a chronic inflammatory gut syndrome characterized by a pattern of relapse and remission and a wide variety of local and/or disseminated bowel affects. Due to chronic inflammation and damage to gastrointestinal wall, CD patients are at an elevated risk of malabsorptive vitamin deficiency, in particular, involving the vitamins folate (B9) and colbalamin (B12).

In certain genetically predisposed patients CD can be attributed to infection by Mycobacterium avium subspecies paratuberculosis (MAP). MAP is the known causative agent of Johne’s disease in cattle and other ruminants, a disease characterized by chronic gut inflammation.

Biologics, such as anti-TNFalpha antibodies used to treat CD in humans, fail to improve symptoms in nearly 50% of human patients. And anti-TNFalpha can exacerbate MAP infection in tissue culture. 

Vaccaro et al. analyzed the effects of folate and vitamin B12 on MAP infections and the related inflammatory response. They examined the effect of folate and B12 on apoptotic activity of macrophages, as well as the effect of these vitamins on MAP-infected macrophages from CD patients. Vitamin levels were measured in ex vivo plasma from CD patients, both those infected with MAP and those with no MAP infection. Expression of IL-1beta and TNFa, markers for apoptosis and viability, were measured in MAP-infected macrophages grown in folate and B12-deficient medium.

Results showed significantly lower plasma levels of folate and B12 in MAP-infected patients, compared to MAP-negative CD patients. Decreased folate and B12 led to lowered macrophage apoptosis in MAP-infected patients. IL-1beta and TNFalpha were upregulated in folate and B12 deprivation during MAP infection, while supplementing these pro-inflammatory cytokines increased macrophage infection. Folate and B12 were deemed to be key factors affecting cell survival and inflammation during MAP infection.

Keywords:  Crohn's disease, cd, map, folate, cobalamin, vitamin deficiency in CD, paratuberculosis