Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota.
OBJECTIVE
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.
Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA. mmalo@partners.org
M S
MS
Malo
S Nasrin
SN
Alam
G
G
Mostafa
S J
SJ
Zeller
P V
PV
Johnson
N
N
Mohammad
K T
KT
Chen
A K
AK
Moss
S
S
Ramasamy
A
A
Faruqui
S
S
Hodin
P S
PS
Malo
F
F
Ebrahimi
B
B
Biswas
S
S
Narisawa
J L
JL
Millán
H S
HS
Warren
J B
JB
Kaplan
C L
CL
Kitts
E L
EL
Hohmann
R A
RA
Hodin
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D006088:Gram-Negative Aerobic Bacteria / Q000302:isolation & purification; D006089:Gram-Negative Anaerobic Bacteria / Q000302:isolation & purification; D006706:Homeostasis / Q000502:physiology; D007421:Intestine, Small / Q000201:enzymology* / Q000382:microbiology*; D054892:Metagenome / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development
D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D000469:Alkaline Phosphatase