B12 and the Benefits of Good Gut Residents

By Dr. Zeena Nackerdien,
Rockefeller University, New York., U.S.A.
When their varying symptoms are finally given a name by a physician, most patients have difficulty wrapping their minds around those two words: “pernicious anaemia (PA)”. The causes that may explain and improve treatment of the effects of vitamin B12 deficiency, a hallmark of PA, are products of ongoing research and discussion on the PA web site and other forums1-4. What does the family of structurally related compounds collectively known as vitamin B12 have to do with the bacteria in our gut? Jeffrey Gordon (M.D.), Director for the Center of Genome Sciences at Washington University in St. Louis, estimates that the number of bacteria colonizing our body surfaces exceeds the total number of our own cells by 10-fold and the majority of those bacteria reside in the gut (10-100trillion!)5. It is perhaps surprising to learn that we cannot make our own B12 and rely on our “gut residents” or bacteria associated with our diet to produce B12.
B12 production is a complex process, involving in part the breakdown of a co-factor derived from another vitamin, B2 (riboflavin), to complete its synthesis6. The cannibalization of a co-factor from one vitamin to produce another vitamin is rare according to the discoverers of this pathway at the Massachusetts Institute of Technology 6. PA patients produce antibodies against stomach parietal cells as well as intrinsic factor, a binding protein involved in the intestinal absorption of B12 1,7. One consequence is autoimmune gastritis. An association between infectious agents and PA-related gastritis has been reported in many studies.
gut residents b12
A mouse colon infected with the bacterium Citrobacter Rodentium, (dark purple dots). The Hematoxylin and eosin-stained section provided by J.A. Guttman (Simon Fraser University, Canada) and B. Brett Finlay (University of British Columbia, Canada).
With a few exceptions, most experts think that the bacterium associated with stomach ulcers, Helicobacter pylori8, influences the absorption of iron and vitamin B12 9-12. A clinical case has been reported in which pernicious anaemia “clustered” with other metabolic derangements and infection caused by a diploid fungus, Candida 13. Another report implicates bacterial overgrowth of the small intestine in vitamin B12 malabsorption 14.
There is consensus on the merits of unraveling the microbial ecology of the human gastrointestinal tract in order to gauge the advantages of diet supplementation with prebiotics (nondigestable carbohydrates that can be fermented by bacteria) and with probiotics or beneficial bacteria. Positive effects of probiotics have been demonstrated for several chronic diseases including Helicobacter-induced gastritis, irritable bowel syndrome and inflammatory bowel diseases15.
For ingested probiotics to aid PA patients in maintaining normal B12 levels, these bacteria must survive transit through the gastrointestinal tract. Some probiotics found in yogurt and kefir survive gut passage and stimulate the immune system 16,17 better than other strains18. Interestingly, some studies show that dairy propionibacteria have a remarkable tolerance to the human upper gastrointestinal tract and an ability to adhere to intestinal epithelia (in vitro studies show improved adherence using combinations of probiotic bacteria).19,20
Propionibacteria can be found in the soil, vegetables, fermented dairy products like kefir and Swiss-type cheeses19. Some of the beneficial effects claimed for specific strains of propionibacteria are stimulation of “good” bacteria such as bifidobacteria and the beneficial modification of the metabolic activities of intestinal microflora 19-21.
While no single bacterium can be a panacea for PA, the addition of another member to the family of “good gut residents” (e.g. Lactobacillus, Bifidobacteria,Bacteroides) may provide symptomatic relief to some patients.
  1. http://enwikipedia.org/wiki/Pernicious_anemia.
  2. Abularrage CJ, Sidawy AN, White PW, Aidinian G, Dezee KJ, Weiswasser JM, Arora S. Effect of folic acid and vitamins B6 and B12 on microcirculatory vasoreactivity in patients with hyperhomocysteinemia. Vasc Endovascular Surg 2007;41(4):339-45.
  3. Don’t underestimate anemia. Johns Hopkins Med Lett Health After 50 2007;19(2):3
  4. Akinyanju OO, Okany CC. Pernicious anaemia in Africans. Clin Lab Haematol 1992;14(1):33-40.
  5. http://gordonlab.wustl.edu/.
  6. Taga ME, Larsen NA, Howard-Jones AR, Walsh CT, Walker GC. BluB cannibalizes flavin to form the lower ligand of vitamin B12. Nature 2007;446 (7134):449-53.
  7. Zimhony O. Pernicious anemia. N Engl J Med 1998;338(14):995.
  8. Andres E, Federici L, Affenberger S, Vidal-Alaball J, Loukili NH, Zimmer J, Kaltenbach G. B12 deficiency: a look beyond pernicious anemia. J Fam Pract 2007;56(7):537-42.
  9. Annibale B, Lahner E, Bordi C, Martino G, Caruana P, Grossi C, Negrini R, Delle Fave G. Role of Helicobacter pylori infection in pernicious anaemia. Dig Liver Dis 2000;32(9):756-62.
  10. Dierkes J, Ebert M, Malfertheiner P, Luley C. Helicobacter pylori infection, vitamin B12 and homocysteine. A review. Dig Dis 2003;21(3):237-44.
  11. Dixon MF. Autoimmune reactions in type A and H. pylori gastritis. Helicobacter 1998;3(3):222.
  12. Djurkov VG, Grudeva-Popova JG, Houbavenska IN. A study of Helicobacter pylori infection in patients with pernicious anemia. Folia Med (Plovdiv) 2000;42(2):23-7.
  13. Manz B, Scholz GH, Willgerodt H, Haustein UF, Nenoff P. Autoimmune polyglandular syndrome (APS) type 1 and candida onychomycosis. Eur J Dermatol 2002;12(3):283-6.
  14. Bondarenko VM, Lykova EA, Matsulevich TV. [Microecological aspects of small intestinal bacterial
    overgrowth syndrome]. Zh Mikrobiol Epidemiol Immunobiol 2006(6):57-63.
  15. Broekaert IJ, Walker WA. Probiotics and chronic disease. Clin.Gastroenterol 2006;40(3):270-274.
  16. Elli M, Callegari ML, Ferrari S, Bessi E, Cattivelli D, Soldi S, Morelli L, Gouppil Feuillerat N, Antoine JM.Survival of yogurt bacteria in the human gut. Appl. Environ Microbiol. 2006;72(7):5113-5117.
  17. Vinderola G, Perdigon G, Duarte J, Farnworth E, Matar C. Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation. J. Dairy Res. 2006;73(4):472-479.
  18. Prilassnig M, Wenisch C, Daxboeck F, Feierl G. Are probiotics detectable in human feces after oral uptake by healthy volunteers? Wien Klin Wochenschr 2007;119(15-16):456-62.
  19. Zarate G, Gonzalez S, Chaia AP. Assessing survival of dairy propionibacteria in gastrointestinal conditions and adherence to intestinal epithelia. Methods Mol Biol 2004;268:423-32.
  20. Zarate G, Morata de Ambrosini VI, Chaia AP, Gonzalez SN. Adhesion of dairy propionibacteria to intestinal epithelial tissue in vitro and in vivo. J Food Prot 2002;65(3):534-9.

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