Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota
- M S Malo1,
- S Nasrin Alam1,
- G Mostafa1,
- S J Zeller2,
- P V Johnson2,
- N Mohammad1,
- K T Chen1,
- A K Moss1,
- S Ramasamy1,
- A Faruqui1,
- S Hodin1,
- P S Malo1,
- F Ebrahimi1,
- B Biswas1,
- S Narisawa3,
- J L Millán3,
- H S Warren4,
- J B Kaplan5,
- C L Kitts6,
- E L Hohmann2,
- R A Hodin1
- 1Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Massachusetts, USA
- 2Infectious Disease Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Massachusetts, USA
- 3Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, California, USA
- 4Infectious Disease Unit, Departments of Pediatrics and Medicine, Massachusetts General Hospital, Harvard Medical School, Massachusetts, USA
- 5Department of Oral Biology, New Jersey Dental School, New Jersey, USA
- 6Environmental Biotechnology Institute, California Polytechnic State University, California, USA
- Correspondence to M S Malo, Department of Surgery, Massachusetts General Hospital, Jackson 812, 55 Fruit Street, Boston, MA 02114, USA;
Contributors Study concept and theory (MSM, RAH); research design (MSM, RAH, ELH, SHW, CLK); data acquisition (MSM, GM, SNA, SJZ, PVJ, CLK, NM, KTC, AKM, AF, SH, PSM, FE, BB, SN); data analyses and interpretation (MSM, RAH, ELH, SHW, CLK, JBK, JLM, SN, SR); statistical analyses (MSM, RAH, ELH, SHW, JBK, CLK); drafting of the manuscript (MSM, RAH, ELH); critical review of the manuscript for important intellectual content (all authors); obtained funding (RAH, MSM); approval of the manuscript (all authors); study supervision (RAH, MSM).
- Revised 25 June 2010
- Accepted 29 June 2010
Background and aims The intestinal microbiota plays a critical role in maintaining human health; however, the mechanisms governing the normal homeostatic number and composition of these microbes are largely unknown. Previously it was shown that intestinal alkaline phosphatase (IAP), a small intestinal brush border enzyme, functions as a gut mucosal defence factor limiting the translocation of gut bacteria to mesenteric lymph nodes. In this study the role of IAP in the preservation of the normal homeostasis of the gut microbiota was investigated.
Methods Bacterial culture was performed in aerobic and anaerobic conditions to quantify the number of bacteria in the stools of wild-type (WT) and IAP knockout (IAP-KO) C57BL/6 mice. Terminal restriction fragment length polymorphism, phylogenetic analyses and quantitative real-time PCR of subphylum-specific bacterial 16S rRNA genes were used to determine the compositional profiles of microbiotas. Oral supplementation of calf IAP (cIAP) was used to determine its effects on the recovery of commensal gut microbiota after antibiotic treatment and also on the colonisation of pathogenic bacteria.
Results IAP-KO mice had dramatically fewer and also different types of aerobic and anaerobic microbes in their stools compared with WT mice. Oral supplementation of IAP favoured the growth of commensal bacteria, enhanced restoration of gut microbiota lost due to antibiotic treatment and inhibited the growth of a pathogenic bacterium (Salmonella typhimurium).
Conclusions IAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections.
- Antibiotic-associated diarrhoea
- gut mucosal defence
- antibiotic therapy
- bacterial pathogenesis
- gut inflammation
Funding This work was supported by NIH grants R01DK050623 and R01DK047186 to RAH, a Junior Faculty Award to MSM from the MGH Department of Surgery and a Grand Challenge Exploration Grant from the Bill and Melinda Gates Foundation to MSM.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.