PMID- 35199834 OWN - NLM STAT- MEDLINE DCOM- 20240201 LR - 20240201 IS - 1541-6100 (Electronic) IS - 0022-3166 (Print) IS - 0022-3166 (Linking) VI - 152 IP - 6 DP - 2022 Jun 9 TI - DHA Supplementation Attenuates Inflammation-Associated Gene Expression in the Mammary Gland of Lactating Mothers Who Deliver Preterm. PG - 1404-1414 LID - 10.1093/jn/nxac043 [doi] AB - BACKGROUND: In a randomized trial of DHA supplementation to lactating mothers who delivered preterm, there were significant increases in DHA status in the mother and her infant. OBJECTIVES: Our objective here was to characterize the mammary gland transcriptomes from the above study. We hypothesized that proinflammatory gene expression would be attenuated in the increased DHA group compared with the standard DHA group. METHODS: In the original trial, mothers delivering at <29 wk gestation at the University of Cincinnati Medical Center and intending to express their milk were randomly assigned to supplementation with 200 mg/d DHA (standard group: STD) or 1000 mg/d DHA (experimental group: EXP) within 7 d of delivery. Here, we conducted RNA-seq transcriptome analysis of n = 5 EXP and n = 4 STD extracellular mammary mRNA samples extracted from the fat layer of milk samples obtained 4 wk postenrollment. Transcripts were assessed for differential expression (false discovery rate adjusted P value <0.05) and clustering between EXP compared with STD groups. Ontological analysis of all differentially expressed genes (DEGs) was performed with Toppcluster. RESULTS: There were 409 DEGs. We observed 5 main groups of biological processes that were upregulated, including those associated with improved immune regulation and management of oxidative stress; and 3 main groups of biological processes that were downregulated, including 1 associated with immune dysregulation. For example, we observed upregulation of inflammation-inhibiting genes including NFKB inhibitor alpha (NFKBIA; fold-change (FC), adjusted P value: FC = 1.70, P = 0.007) and interleukin-18 binding protein (IL18BP: FC = 2.2, adjusted P = 0.02); and downregulation of proinflammatory genes including interleukin 7 receptor (IL7R: FC = -1.9, adjusted P = 0.02) and interleukin 1 receptor like 1 (IL1RL1: FC = -13.0, adjusted P = 0.02). CONCLUSIONS: Increased DHA supplementation during lactation can modulate the expression of inflammation-related genes within the mammary gland. This might translate to milk composition with a more optimal inflammasome profile. Future research with a larger clinical trial and greater interrogation of clinical outcomes is warranted. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition. FAU - Adams, Joselyn M AU - Adams JM AD - Department of Rehabilitation, Exercise, and Nutritional Sciences, University of Cincinnati College of Allied Health Sciences, Cincinnati, OH, USA. FAU - Valentine, Christina J AU - Valentine CJ AD - Department of Neonatology, Banner University Medical Center, The University of Arizona, Tucson, AZ, USA. FAU - Karns, Rebekah A AU - Karns RA AD - Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. FAU - Rogers, Lynette K AU - Rogers LK AD - Center for Perinatal Research, Nationwide Children's Hospital, Columbus, OH, USA. FAU - Murase, Masahiko AU - Murase M AD - Department of Neonatology, Showa University Hospital, Shinagawa City, Tokyo, Japan. FAU - Fowler, Grace N AU - Fowler GN AD - Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Nommsen-Rivers, Laurie A AU - Nommsen-Rivers LA AUID- ORCID: 0000-0003-3213-7186 AD - Department of Rehabilitation, Exercise, and Nutritional Sciences, University of Cincinnati College of Allied Health Sciences, Cincinnati, OH, USA. LA - eng GR - R01AT006880/NH/NIH HHS/United States GR - KL2TR000078/University of Cincinnati/ PT - Clinical Trial PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 25167-62-8 (Docosahexaenoic Acids) SB - IM MH - Female MH - Humans MH - Infant MH - Infant, Newborn MH - *Dietary Supplements MH - *Docosahexaenoic Acids/metabolism/therapeutic use MH - Gene Expression/drug effects MH - *Inflammation/diet therapy/genetics/metabolism MH - Lactation MH - Mammary Glands, Human/drug effects/metabolism MH - Milk, Human/chemistry MH - Mothers PMC - PMC9178958 OTO - NOTNLM OT - RNA sequencing OT - cytokine OT - docosahexaenoic acid OT - human milk OT - inflammation OT - lactation physiology OT - omega-3 fatty acids OT - premature birth OT - transcriptome EDAT- 2022/02/25 06:00 MHDA- 2022/06/14 06:00 PMCR- 2022/02/24 CRDT- 2022/02/24 08:43 PHST- 2021/10/07 00:00 [received] PHST- 2022/01/25 00:00 [revised] PHST- 2022/02/21 00:00 [accepted] PHST- 2022/02/25 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/02/24 08:43 [entrez] PHST- 2022/02/24 00:00 [pmc-release] AID - S0022-3166(22)00640-X [pii] AID - nxac043 [pii] AID - 10.1093/jn/nxac043 [doi] PST - ppublish SO - J Nutr. 2022 Jun 9;152(6):1404-1414. doi: 10.1093/jn/nxac043.