Neutrophil homeostasis regulated by the microbiota in neonates mice

A Nature Medicine paper by Hitesh S Deshmukh and colleagues from the Division of Neonatology, Childrens Hospital of Philadelphia, Pennsilvania, USA reports an important aspect to the use of antibiotics in the integrity of the immune system in the newborn. Neonatal colonization by microbes, which begins immediately after birth, is influenced by gestational age and the mother’s microbiota and is modified (among others) by exposure to antibiotics. In neonates, prolonged duration of antibiotic therapy is associated with increased risk of late-onset sepsis, a disorder controlled by neutrophils.

A role for the microbiota in regulating neutrophil development and susceptibility to sepsis in the neonate was investigated in pregnant mice exposed to antibiotics in drinking water, to limit transfer of maternal microbes to the neonates. This decreased the total number and composition of microbes in the intestine of the neonates and was associated with decreased numbers of circulating and bone marrow neutrophils and granulocyte/macrophage–restricted progenitor cells in the bone marrow of antibiotic-treated and germ-free neonates, resulting in impaired host defense and increased susceptibility to Escherichia coli K1 and Klebsiella pneumoniae sepsis in antibiotic-treated neonates. Transfer of a normal microbiota into antibiotic-treated neonates induced IL-17 production again and restored resistance to sepsis.

An editorial for the paper by Ajitha Thanabalasuriar & Paul Kubes in the same journal comments this paper with respect to its relevance also for human physiology and pathophysiology: It seems that just having bacteria in the gut is not enough; instead, the dominant class of bacteria is crucial: diminishing Gammaproteobacteria colonization of the neonate early in life is key to developing susceptibility to blood-borne infections. One could envision a probiotic treatment based on the overall microbiota composition of a healthy baby to prevent disease in vulnerable newborns. This potential probiotic treatment could be extended to vulnerable neonates to improve health without subjecting them to late onset sepsis and potential chronic inflammatory diseases later in life.

  1. Deshmukh HS, Liu Y, Menkiti OR, Mei J, Dai N, O’Leary CE, Oliver PM, Kolls JK, Weiser JN, Worthen GS. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med. 2014 May;20(5):524-30. doi: 10.1038/nm.3542.
  2. Thanabalasuriar A, Kubes P. Neonates, antibiotics and the microbiome. Nat Med. 2014 May 7;20(5):469-70. doi: 10.1038/nm.3558.neo
Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.