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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #336366

Title: Formula diet driven microbiota shifts tryptophan metabolism from serotonin to tryptamine in neonatal porcine colon

Author
item SARAF, MANISH - Arkansas Children'S Nutrition Research Center (ACNC)
item PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC)
item BOWLIN, ANNE - Arkansas Children'S Nutrition Research Center (ACNC)
item MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC)
item LEROITH, TANYA - Virginia-Maryland Regional College Of Veterinary Medicine (VMRCVM)
item CHINTAPALLI, SREE - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)
item Badger, Thomas
item YERUVA, LAXMI - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Microbiome
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2017
Publication Date: 7/14/2017
Citation: Saraf, M.K., Piccolo, B.D., Bowlin, A.K., Mercer, K.E., Leroith, T., Chintapalli, S.V., Shankar, K., Badger, T.M., Yeruva, L. 2017. Formula diet driven microbiota shifts tryptophan metabolism from serotonin to tryptamine in neonatal porcine colon. BMC Microbiome. 5:77. doi:10.1186/s40168-017-0297-z.

Interpretive Summary: Breastfeeding has been shown to convey many positive metabolic and health benefits to infants, and these outcomes can be persistent into childhood and beyond. The precise mechanisms by which postnatal diets (i.e., breastfeeding vs. formula feeding) impact the body's tissues and function remain to be fully elaborated, prompting the current study that aimed to determine if breast milk feeding has any advantage in terms of gut development and immune function. To address these questions, we used a neonatal piglet model breastfed on the sow, comparing to dairy milk-based or soy milk based formulas. This study determined that formula diets reduce diversity of the distal colon microbiome (bacteria and other microbes that naturally reside in the gut), and possibly impact immune response. Gut bacteria such as Streptococcus, Blautia, Citrobacter, Butrycimonas, Parabacteroides, Lactococcus genera were increased in formula-fed relative to sow-fed piglets. No significant morphological changes were noted in the distal colon, suggesting that formula feeding did not have a major impact on colon anatomy. By examining the make-up of the bacteria in the gut, a novel finding was that postnatal diet could potentially impact metabolism of the amino acid tryptophan and possibly the neurotransmitter serotonin pathway. Consistent with this, in comparison to the sow-fed group, intestinal serotonin levels were reduced and a known bacterial metabolite (tryptamine) levels were increased in formula-fed piglets. Several reports indicate that dysfunction of the serotonergic pathway can impact the integrity of the host immune system, and tryptamine increases levels of histamine which could impact susceptibility to allergies. If these results in piglets recapitulate in human infants, these early changes in gastrointestinal and immune system development due to formula feeding could have long-term health consequences. For instance, the current results suggest that breastfeeding maintains optimal serotonin and histamine status in the gut in terms of regulating the immune system, when compared to typical formula feeding regimens. The study also highlights the importance of characterizing the consequences of early diet on long-term changes in the gut microbiome, immune system and host physiology.

Technical Abstract: The gut microbiota of breast-fed and formula-fed infants differ significantly, as do the risks for allergies, gut dysfunction and upper respiratory tract infections. The connections between breast milk, various formulas, and the profiles of gut bacteria to these childhood illnesses, as well as the mechanisms underlying the effects, are not well understood. We investigated distal colon microbiome by 16S RNA amplicon sequencing, morphology by histomorphometry, immune response by cytokine expression and tryptophan metabolism in a pig model in which piglets were sow-fed, or fed soy or dairy milk-based formula from postnatal day (PND) 2 to 21. Formula feeding significantly (p<0.05) altered the colon microbiome relative to the sow feeding. A significant reduction in microbial diversity was noted with formula groups in comparison to sow-fed. Streptococcus, Blautia, Citrobacter, Butrycimonas, Parabacteroides, Lactococcus genera were increased with formula feeding relative to sow feeding. In addition, relative to sow feeding, Anaerotruncus, Akkermansia, Enterococcus, Acinetobacter, Christensenella, Holdemania were increased in milk-fed piglets, and Biliophila, Ruminococcus, Clostridium were increased in soy fed piglets. No significant gut morphological changes were noted. However, higher cytokine mRNA expression (BMP4, CCL11, CCL21) was observed in the distal colon of formula groups. Formula feeding reduced enterochromaffin cell number and serotonin, but increased tryptamine levels relative to sow feeding. Our data confirm that formula diet alters the colon microbiome and appears to shift tryptophan metabolism from serotonin to tryptamine, which may lead to greater histamine levels and risk of allergies in infants.