Abstract：Objective To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC). Methods Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota. Results Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora. Conclusions Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.
WANG Shan-Shan,CAI Jin-Yang,SHI Ai-Wu et al. Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis[J]. CJCP, 2023, 25(8): 855-863.
Kling PJ, Hutter JJ. Hematologic abnormalities in severe neonatal necrotizing enterocolitis: 25 years later[J]. J Perinatol, 2003, 23(7): 523-530. PMID: 14566346. DOI: 10.1038/sj.jp.7210983.
Ragazzi S, Pierro A, Peters M, et al. Early full blood count and severity of disease in neonates with necrotizing enterocolitis[J]. Pediatr Surg Int, 2003, 19(5): 376-379. PMID: 12756597. DOI: 10.1007/s00383-003-1014-5.
Huang K, Mukherjee S, Desmarais V, et al. Targeting the PXR-TLR4 signaling pathway to reduce intestinal inflammation in an experimental model of necrotizing enterocolitis[J]. Pediatr Res, 2018, 83(5): 1031-1040. PMID: 29360809. PMCID: PMC5959752. DOI: 10.1038/pr.2018.14.
Yan X, Cao Y, Chen W, et al. Peptide (tat(48-60)) YVEEL protects against necrotizing enterocolitis through inhibition of Toll-like receptor 4-mediated signaling in a phosphatidylinositol 3-kinase/AKT dependent manner[J]. Front Nutr, 2022, 9: 992145. PMID: 36299988. PMCID: PMC9590307. DOI: 10.3389/fnut.2022.992145.
Barnett-Vanes A, Sharrock A, Birrell MA, et al. A single 9-colour flow cytometric method to characterise major leukocyte populations in the rat: validation in a model of LPS-induced pulmonary inflammation[J]. PLoS One, 2016, 11(1): e0142520. PMID: 26764486. PMCID: PMC4713146. DOI: 10.1371/journal.pone.0142520.
