Bacterial and fungal adaptations in cecum and distal colon of piglets fed dairy-based milk formula in comparison to human milk

Authors: ELOLIMY, AHMED - University Arkansas For Medical Sciences (UAMS); ROSA, FERNANDA - University Arkansas For Medical Sciences (UAMS); TRIPP, PATRICIA - Arkansas Children'S Nutrition Research Center (ACNC); BOWLIN, ANNE - University Arkansas For Medical Sciences (UAMS); RANDOLPH, CHRISTOPHER - Arkansas Children'S Hospital; ROBESON, MIKE - University Arkansas For Medical Sciences (UAMS); Yeruva, Laxmi

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/8/2022
Publication Date: 3/23/2022
Citation: Elolimy, A., Rosa, F., Tripp, P., Bowlin, A.K., Randolph, C., Robeson, M., Yeruva, V. 2022. Bacterial and fungal adaptations in cecum and distal colon of piglets fed dairy-based milk formula in comparison to human milk. Frontiers in Microbiology. https://doi.org/10.3389/fmicb.2022.801854.
DOI: https://doi.org/10.3389/fmicb.2022.801854

Interpretive Summary: Exclusive breastfeeding is recommended to newborns during the first 6 months of life by the World Health Organization and American Academy of Pediatrics, however dairy-based infant formula is recommended as an alternative nutrition source to human milk. Moreover, studies demonstrated that breastfed infants have a distinct intestinal bacterial composition relative to formula fed infants. Using a piglet model, our group has previously reported differences in the gut bacterial composition of piglets that were human milk fed compared to milk-formula. However, less is known about the fungal and archaeal composition in the gut. To address this knowledge gap, piglets were fed pasteurized human milk (HM) or a dairy-based infant formula (MF) during the first 21 days of life and weaned to solid diet until day 51. We evaluated the bacterial, fungal, and archaeal communities and their gene expression from the large intestine at day 21 and post weaning neonatal diet at day 51. We observed that beneficial bacterial abundance (i.e Lactobacillus sps, Bacteroides) is higher in HM while gram negative bacteria (i.e Proteobacteria and Burkholderiales bacterium) that were associated with inflammation and asthma outcomes were higher in MF fed piglets. For fungal taxa, Aspergillus spp which was associated adiposity and weight gain and increased incidence of rhinitis was higher in MF relative to HM group. Archaea taxa presence to health outcomes has been understudied thus, future studies are needed to better understand the importance of archaea in health. However, it is possible that interkingdom communication occurs between bacteria, fungi and archaea species. Overall, our findings indicate that human milk diet associated microbial changes are beneficial to the infants health outcomes.

Technical Abstract: Exclusive breastfeeding is recommended to newborns during the first 6 months of life, however dairy-based infant formula is recommended as an alternative nutrition source to human milk. Several studies demonstrated that breastfed infants have a different gut bacterial composition relative to formula fed. Additionally, animal models have shown that human mik-fed piglets had a distinct gut microbial composition and microbial proteins compared to milk-formula fed piglets. However, the gut fungal and archaeal composition and the interactions with the bacterial community in breastfed compared to formula fed inafnts remains to be investigated. In the attempt to evaluate such differences we used an animal model to perform a metagenomics analysis on the cecal and distal colon contents of neonatal piglets fed pasteurized human milk (HM) or a dairy-based infant formula (MF) during the first 21 days of life. At postnatal day 21 (PND 21), a subset of piglets from each diet group (n = 11/group) were euthanized and cecal and distal colon contents were collected for further metagenomics analysis. The remaining piglets in each group were weaned to a solid diet and euthanized at PND 51 (n = 13/group). At PND 51, cecal and distal colon contents were also collected for further metagenomics analysis. The differential taxonomic composition of bacteria, fungi, and archeae, as well as the predicted functional gene profiling were evaluated using the MicrobiomeAnalyst software. At PND 21, among other bacterial species the cecal lumen of MF-fed group had higher abundance of Bacteroides thetaiotaomicron and Bacteroides uniformis. Cecal fungal composition was impacted by HM feeding with greater abundance of fungal species Yarrowia lipolytica, Laccaria bicolor, Malassezia globose relative to the MF-fed group. At the archaeal level, among other species the abundance of Methanocorpusculum labreanum was greater in the MF relative to the HM fed group. The distal colon of HM fed piglets had greater abundance of Lactobacillus johnsonii compared to the MF group at PND 21. At the fungal species level, Botryotinia fuckeliana and Ajellomyces capsulatus were greater abundant in the HM fed group. In contrast, MF group had greater Cenarchaeum symbiosum archaeal abundance in the distal colon at 21 days. Persistent effects of the neonatal diets were observed at PND 51, whereas alpha- and beta-diversity differences were detected for bacterial, fungal, and archaeal species in the cecum and distal colon. Overall, our findings indicate that neonatal diet impacts the large intestinal microbial community during the exclusive milk feeding period, as well as after the introduction of the complementary food.