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Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are compounds mostly produced by the microbiome through various metabolic pathways and play an indispensable role in connecting the microbiome and the adaptive immune system. This review aims to summarise recent findings regarding the intricate relationship between SCFAs, the gut microbiome, and T lymphocytes with a focus on early life interactions. The paper discusses factors affecting the establishment of the neonatal microbiome, especially human milk versus formula milk, and how these influence SCFA concentrations in feces, which in turn directly impact T cell development and function. Despite recent advances in understanding the role of gut microbiome derived SCFAs in adults, a significant knowledge gap remains in translating these findings to neonates and exploring the utility of SCFAs as a potential therapeutic intervention in inflammatory complications of preterm and term neonates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This review highlights potential therapeutic applications of short-chain fatty acids (SCFAs) in neonatal care, particularly in preventing and treating inflammatory conditions. This could lead to new treatment strategies for conditions like NEC and other immune-mediated disorders in neonates.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>By identifying significant knowledge gaps in neonatal SCFA research, this review helps future investigations toward understanding SCFA mechanisms specifically in neonates, potentially leading to age-appropriate therapeutic interventions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Understanding the relationship between early-life factors (such as feeding methods and microbiome development) and immune system development through SCFAs could inform public health policies and recommendations for infant nutrition and care practices.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04075-0","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T03:04:23Z","timestamp":1746068663000},"page":"1698-1706","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Short-chain fatty acids\u2014a key link between the gut microbiome and T-lymphocytes in neonates?"],"prefix":"10.1038","volume":"99","author":[{"given":"Tram N. 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