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Title: The microbiome, intestinal function, and arginine metabolism of healthy Indian women are different from those of American and Jamaican women

Author
item KAO, CHRISTINA - Children'S Nutrition Research Center (CNRC)
item COPE, JULIA - Texas Children'S Hospital
item HSU, JEAN - Children'S Nutrition Research Center (CNRC)
item DWARKANATH, PRATIBHA - St John'S National Academy Of Health Sciences
item KARNES, JEFFREY - Children'S Nutrition Research Center (CNRC)
item LUNA, RUTH - Texas Children'S Hospital
item HOLLISTER, EMILY - Texas Children'S Hospital
item THAME, MINERVA - University Of The West Indies
item KURPAD, ANURA - St John'S National Academy Of Health Sciences
item JAHOOR, FAROOK - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2016
Publication Date: 3/9/2016
Citation: Kao, C.C., Cope, J.L., Hsu, J.W., Dwarkanath, P., Karnes, J.M., Luna, R.A., Hollister, E.B., Thame, M.M., Kurpad, A.V., Jahoor, F. 2016. The microbiome, intestinal function, and arginine metabolism of healthy Indian women are different from those of American and Jamaican women. Journal of Nutrition. doi:10.3945/jn.115.227579.

Interpretive Summary: Arginine is a compound that is very important for normal growth of a baby during pregnancy because it is needed to make new body proteins and also to make nitric oxide, a compound that is needed for the pregnant mother's blood to flow freely to the growing baby to deliver sufficient nutrition. In studies of American, Jamaican and Indian women, we found that both American and Jamaican women increase the amount of arginine and nitric oxide during pregnancy, but Indian women did not. Most importantly, the Indian women who produced less arginine had smaller babies and a high number of those babies were low birth weight babies. This is a big problem in the world because low birth weight babies are sicker, have a higher death rate and when they grow up to be adults, they have a higher rate of diabetes and heart disease. We therefore wanted to find out why pregnant Indian women were making less arginine and wondered whether this may be a problem with Indian women on the whole, regardless of whether they were pregnant or not. We studied arginine and nitric oxide in healthy normal weight Indian, American and Jamaican women who were not pregnant. Compared to American women, Indian women had less arginine available to make protein and nitric oxide because they were converting a lot of their arginine to another compound named ornithine. Indian women were also making less arginine. We also found that Indian women made less citrulline than American and Jamaican women and broke down more arginine to ornithine. Their gut capacity to absorb nutrition into the body was also much less than American and Jamaican women. The type of bacteria living in their gut was very different from American and Jamaican women and these types of bacteria were related to their diet, their decreased gut function, and the amount of arginine they were making. This study suggests that the bacteria living in the gut of Indian women is contributing to a decrease in the amount of arginine available to the rest of their body. Because a woman gets arginine from two sources, the amount she makes in her body plus the amount she gets from the protein in her meals, the findings of this study suggest that adult Indian women who are thinking of becoming pregnant should eat more protein so they will have a sufficient amount for their growing baby.

Technical Abstract: Indian women have slower arginine flux during pregnancy compared with American and Jamaican women. Arginine is a semi-essential amino acid that becomes essential during periods of rapid lean tissue deposition. It is synthesized only from citrulline, a nondietary amino acid produced mainly in the gut. The gut is therefore a key site of arginine and citrulline metabolism, and gut microbiota may affect their metabolism. The objective of this study was to identify differences in the gut microbiota of nonpregnant American, Indian, and Jamaican women and characterize the relations between the gut microbiota, gut function, and citrulline and arginine metabolism. Thirty healthy American, Indian, and Jamaican women (n = 10/group), aged 28.3 +/- 0.8 y, were infused intravenously with [guanidino-15N2]arginine, [5,5-2H2]citrulline, and [15N2]ornithine and given oral [U-13C6]arginine in the fasting and postprandial states. Fecal bacterial communities were characterized by 16S rRNA gene sequencing. In the fasting state, Indian women had lower citrulline flux than did American and Jamaican women [7.0 +/- 0.4 compared with 9.1 +/- 0.4 and 8.9 +/- 0.2 umol/kg fat-free mass (FFM)/h, P = 0.01] and greater enteral arginine conversion to ornithine than did American women (1.4 +/- 0.11 compared with 1.0 +/- 0.08 umol/kg FFM/h, P = 0.04). They also had lower mannitol excretion than American and Jamaican women (154 +/- 37.1 compared with 372 +/- 51.8 and 410 +/- 39.6 mg/6 h, P < 0.01). Three dominant stool community types characterized by increased abundances of the genera Prevotella, Bacteroides, and Bacteroides with Clostridium were identified. Indian women had increased mean relative abundances of Prevotella (42%) compared to American and Jamaican women (7% and < 1%, P = 0.03) which were associated with diet, impaired intestinal absorptive capacity, and arginine flux. These findings suggest that dysregulated intestinal function and a unique gut microbiome may contribute to altered arginine metabolism in Indian women.