{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:04:30Z","timestamp":1790193870281,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Charles H. and Judy Hood Family Infant Health Research Program","award":["T32HD098061"],"award-info":[{"award-number":["T32HD098061"]}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development of the National Institutes of Health","doi-asserted-by":"publisher","award":["T32HD098061"],"award-info":[{"award-number":["T32HD098061"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Short-chain fatty acids (SCFAs), microbial metabolites, have been minimally studied in neonatal pathophysiology but have been associated with disease outcomes in adults. The objective of this manuscript was to determine if SCFA levels in maternal breastmilk (BM) and stool from preterm neonates impacted the risk of neonatal morbidities. Methods: SCFA levels were quantified by liquid chromatography with tandem mass spectrometry on maternal BM and neonatal stool for preterm infants &lt; 28 weeks\u2019 gestation (N = 72) on postnatal days 14 and 28. SCFA levels in BM and stool of infants with and without bronchopulmonary disease (BPD) and retinopathy of prematurity (ROP) were compared. Logistic regression was applied to determine the association between stool acetic acid levels and disease. Results: Acetic, propionic, isobutyric, 2-methylbutyric, and isovaleric acid levels increased in BM and neonatal stool between days 14 and 28. Logistic regression demonstrated an inverse relationship between the quartile of fecal acetic acid level and the odds of BPD but not ROP on days 14 and 28. For each quartile increase in fecal acetic acid, the odds ratio (95% CI) of BPD was 0.41 (0.18, 0.83) for day 14 and 0.28 (0.09, 0.64) for day 28. Conclusions: Low acetic acid levels in the stool of preterm infants are associated with increased odds of BPD. These findings support a relationship between intestinal and pulmonary health in preterm infants.<\/jats:p>","DOI":"10.3390\/nu14122412","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"2412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Decreased Acetic Acid in the Stool of Preterm Infants Is Associated with an Increased Risk of Bronchopulmonary Dysplasia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2366-7409","authenticated-orcid":false,"given":"Lauren C.","family":"Frazer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-5404","authenticated-orcid":false,"given":"William","family":"Yakah","sequence":"additional","affiliation":[{"name":"Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-6126","authenticated-orcid":false,"given":"Camilia R.","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2020030007","DOI":"10.1542\/peds.2020-030007","article-title":"Severity of Bronchopulmonary Dysplasia Among Very Preterm Infants in the United States","volume":"148","author":"Jensen","year":"2021","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3389\/fmed.2015.00090","article-title":"Understanding the Impact of Infection, Inflammation, and Their Persistence in the Pathogenesis of Bronchopulmonary Dysplasia","volume":"2","author":"Balany","year":"2015","journal-title":"Front. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fmed.2017.00024","article-title":"Commentary: Understanding the Impact of Infection, Inflammation and Their Persistence in the Pathogenesis of Bronchopulmonary Dysplasia","volume":"4","author":"Kolls","year":"2017","journal-title":"Front. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12974-017-0943-1","article-title":"Retinopathy of prematurity: Inflammation, choroidal degeneration, and novel promising therapeutic strategies","volume":"14","author":"Rivera","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.siny.2018.08.002","article-title":"Innate and adaptive immunity in necrotizing enterocolitis","volume":"23","author":"Mara","year":"2018","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1111\/j.1651-2227.2010.01973.x","article-title":"The clustering of disorders in infants born before the 28th week of gestation","volume":"99","author":"Leviton","year":"2010","journal-title":"Acta Paediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104074","DOI":"10.1016\/j.jff.2020.104074","article-title":"Human milk oligosaccharides: Shaping the infant gut microbiota and supporting health","volume":"72","author":"Walsh","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zheng, N., Gao, Y., Zhu, W., Meng, D., and Walker, W.A. (2020). Short chain fatty acids produced by colonizing intestinal commensal bacterial interaction with expressed breast milk are anti-inflammatory in human immature enterocytes. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0229283"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"595157","DOI":"10.3389\/fped.2020.595157","article-title":"Acetate Downregulates the Activation of NLRP3 Inflammasomes and Attenuates Lung Injury in Neonatal Mice With Bronchopulmonary Dysplasia","volume":"8","author":"Zhang","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/pr.2017.268","article-title":"Development of severe bronchopulmonary dysplasia is associated with alterations in fecal volatile organic compounds","volume":"83","author":"Berkhout","year":"2018","journal-title":"Pediatr. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307ra152","DOI":"10.1126\/scitranslmed.aab2271","article-title":"Early infancy microbial and metabolic alterations affect risk of childhood asthma","volume":"7","author":"Arrieta","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fenton, T.R., and Kim, J.H. (2013). A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr., 13.","DOI":"10.1186\/1471-2431-13-59"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1542\/peds.91.3.617","article-title":"Score for Neonatal Acute Physiology: A physiologic severity index for neonatal intensive care","volume":"3","author":"Richardson","year":"1993","journal-title":"Pediatrics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/MPG.0000000000000934","article-title":"Factors Determining Optimal Fatty Acid Absorption in Preterm Infants","volume":"62","author":"Martin","year":"2016","journal-title":"J. Pediatric Gastroenterol. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1002\/oby.20901","article-title":"Metabolomic profiles and childhood obesity","volume":"22","author":"Perng","year":"2014","journal-title":"Obesity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v057.i12","article-title":"Building Bivariate Tables: The compare Groups Package for R","volume":"57","author":"Subirana","year":"2014","journal-title":"J. Stat. Softw."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cyto.2017.03.012","article-title":"Antecedents and correlates of blood concentrations of neurotrophic growth factors in very preterm newborns","volume":"94","author":"Leviton","year":"2017","journal-title":"Cytokine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Frau, A., Lett, L., Slater, R., Young, G.R., Stewart, C.J., Berrington, J., Hughes, D.M., Embleton, N., and Probert, C. (2021). The Stool Volatile Metabolome of Pre-Term Babies. Molecules, 26.","DOI":"10.3390\/molecules26113341"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1093\/glycob\/cwt065","article-title":"Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes","volume":"23","author":"Yu","year":"2013","journal-title":"Glycobiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/pr.2014.156","article-title":"Bifidobacterium longum subspecies infantis: Champion colonizer of the infant gut","volume":"77","author":"Underwood","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41586-021-03241-8","article-title":"Multi-kingdom ecological drivers of microbiota assembly in preterm infants","volume":"591","author":"Rao","year":"2021","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nm.3444","article-title":"Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis","volume":"20","author":"Trompette","year":"2014","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7320","DOI":"10.1038\/ncomms8320","article-title":"Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites","volume":"6","author":"Thorburn","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e024974","DOI":"10.1136\/bmjopen-2018-024974","article-title":"Effectiveness of an antenatal maternal supplementation with prebiotics for preventing atopic dermatitis in high-risk children (the PREGRALL study): Protocol for a randomised controlled trial","volume":"9","author":"Cabridain","year":"2019","journal-title":"BMJ Open"},{"key":"ref_26","unstructured":"Prescott, S. (2022, June 01). A Randomised, Double-Blind, Placebo-Controlled Trial to Investigate the Effects of Maternal Dietary Prebiotic Fibre Supplementation, from Early Pregnancy to 6 Months Lactation, on Infant Outcomes of Immune Function and Eczema Diagnosis. Available online: https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=369064&isReview=true."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1038\/cti.2016.17","article-title":"Regulation of immune cell function by short-chain fatty acids","volume":"5","author":"Fachi","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1152\/physrev.2001.81.3.1031","article-title":"Short-chain fatty acids and human colonic function: Roles of resistant starch and nonstarch polysaccharides","volume":"81","author":"Topping","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2021051485","DOI":"10.1542\/peds.2021-051485","article-title":"Use of Probiotics in Preterm Infants","volume":"147","author":"Poindexter","year":"2021","journal-title":"Pediatrics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"667188","DOI":"10.3389\/fnut.2021.667188","article-title":"Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis","volume":"8","author":"Murphy","year":"2021","journal-title":"Front. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2412\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:25Z","timestamp":1760138845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/12\/2412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":30,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["nu14122412"],"URL":"https:\/\/doi.org\/10.3390\/nu14122412","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}