Short chain fatty acids produced by colonizing intestinal commensal bacterial interaction with expressed breast milk are anti-inflammatory in human immature enterocytes

• Published in: PloS one Vol. 15; no. 2; p. e0229283
• Main Authors: Zheng, Nan, Gao, Yanan, Zhu, Weishu, Meng, Di, Walker, W. Allan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.02.2020; Public Library of Science (PLoS)
• Subjects: Acetic acid; Animal sciences; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Authorship; Babies; Bacteria; Bifidobacterium longum subspecies infantis - physiology; Biology; Biology and Life Sciences; Birth weight; Breast; Breast milk; Breastfeeding & lactation; Colon; Enterocolitis; Enterocytes; Enterocytes - cytology; Enterocytes - drug effects; Enterocytes - metabolism; Enzyme Induction - drug effects; Enzymes; Esters; Experiments; Fatty acids; Fatty Acids, Volatile - biosynthesis; Fatty Acids, Volatile - pharmacology; Fetus - microbiology; Fetuses; G protein-coupled receptors; Gastrointestinal diseases; Gene expression; Histone deacetylase; Histone Deacetylases - genetics; Humans; Immunology; Infants; Inflammation; Interleukin-1beta - metabolism; Interleukin-8 - metabolism; Intestine; Intestines - cytology; Intestines - microbiology; Kinases; Laboratories; Legal fees; Low birth weight; Medical research; Medicine and Health Sciences; Mepenzolate; Metabolites; Mice; Milk; Milk, Human - microbiology; Mutagenesis, Insertional - drug effects; Necrosis; Necrotizing enterocolitis; Organoids; Organoids - drug effects; Organoids - metabolism; Pathogenesis; Physical Sciences; Premature infants; Probiotics; Propionic acid; Receptors, G-Protein-Coupled - metabolism; Research and Analysis Methods; Small intestine; Software industry; United States; Beijing China; United States > US; China; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0229283

Necrotizing enterocolitis (NEC) is a devastating intestinal emergency that affects ten percent of very low birth weight premature babies and costs society in both expense and heartache. It is probably caused by an inappropriate interaction of colonizing bacteria with an immature intestine. A possible preventative measure is to feed prematures their mother's expressed breast milk in conjunction with a probiotic. This synbiotic prevention reduces the severity and incidence of this condition. This study was designed to determine the mechanism of the synbiotic effect in human and mouse fetal intestine. Breast milk interacting with a NEC preventative probiotic such as Bifidobacterium infantis can produce increased levels of short chain fatty acids (acetate, propionate and butyrate) (SCFAs). SCFAs are known to be anti-inflammatory in mature enterocytes and immunocytes. Very little is known about their role in immature intestine. When exposed to a human fetal cell line, fetal intestinal organoids and fetal mouse intestine, these SCFAs were anti-inflammatory. Their mechanism of anti-inflammation differed from those reported for mature cells by involving the G-protein coupled receptor (GPR 109A) and inhibiting histone deacetylase 4 and 5. These bacterial metabolites may help explain the synbiotic anti-inflammatory effect of breast milk and probiotics given to premature infants at risk for NEC.