Invited Speaker 49th Nutrition Society of Australia Annual Scientific Meeting 2025

Is colon health promoted by newly discovered gut microbial biosynthesis of vitamin D2? (131691)

David R Fraser 1 , Alex V Chaves 2 , Mark S Rychyn 3 , Rebecca S Mason 2 3
  1. Sydney School of Veterinary Science, The University of Sydney, Sydney, NSW, Australia
  2. School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia
  3. School of Medical Sciences and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia

Many epidemiological studies have reported that vitamin D deficiency and low vitamin D status are associated with inflammatory bowel disease and colon cancer (1). There is considerable evidence that some of the vitamin D, produced in skin by the action of solar ultraviolet light on 7-dehydrocholesterol, when passing in blood through the capillaries of the large intestine, is taken up by cells in the mucosa and metabolized there to 25-hydroxyvitamin D, which is further converted in those cells to the active hormone, 1,25-dihydroxyvitamin D (1). This vitamin D hormone then exerts a paracrine effect on the cells of the mucosal immune system, to prevent noxious invasive activity of the vast array of microbial species involved in fermenting the food residue in the lumen of the large intestine (1). It has also been demonstrated in mice that oral administration of glucuronide conjugates of vitamin D or 25-hydroxyvitamin D are not absorbed in the small intestine so that when they pass into the lumen of the large intestine, they are cleaved by bacterial glucuronidase to release vitamin D and 25-hydroxyvitamin D (2). These vitamin D structures can then be absorbed by the colon mucosa and converted there to 1,25-dihydroxyvitamin D. Thus, vitamin D function in the immune system of the large intestine can be maintained either by delivery of vitamin D from the circulation or by absorption from the lumen contents. We have recently discovered that vitamin D2 (ergocalciferol), is being metabolically produced by anaerobic gut microorganisms in the forestomach of ruminant animals and in the hindgut of mice (3). This is the first demonstration of vitamin D formation by a mechanism other than by the action of ultraviolet light on a steroid precursor. Microbial production of vitamin D2 in the large intestine, is undoubtedly for some function of the organism(s) performing this biosynthesis. Before the endocrine role of vitamin D was discovered, vitamin D had been shown to change the properties of bacterial cell membranes to facilitate the uptake of amino acids and thus promote bacterial growth (3). A symbiotic benefit of microbial biosynthesis of vitamin D2 in the lumen of the colon of the host human could therefore also be contributing to the supply of vitamin D in maintaining its endocrine role in the protective immune system of that organ. Such microbial supply of vitamin D2 to the hindgut would be independent of seasonal variation in vitamin D status in people in temperate regions of the world and would maintain its role in the hindgut immune system. This beneficial function could be facilitated by discovering nutritional strategies for promoting the growth of the microorganisms producing vitamin D2 or by supplying the yet-to-be discovered metabolic precursor in the human diet.

  1. 1. Meeker S, Seamons A, Maggio-Price L & Paik J (2018) World J Gastroenterol 22, 933-948
  2. 2. Goff JP, Koszewski NJ, Haynes JS & Horst RL (2012) Am J Physiol 302, G460-G469
  3. 3. Chaves AV, Rybchyn MS, Mason RS & Fraser DR (2024) Comp Biochem Physiol A 295, 111666