[Effect of Gut Microbiota Homeostasis on Hematopoiesis in a Neonatal Rat Model of Necrotizing Enterocolitis]

Overview

Journal Zhongguo Dang Dai Er Ke Za Zhi

Specialty Pediatrics

Date 2023 Sep 5

PMID 37668035

Authors

Shan-Shan Wang

Jin-Yang Cai

Ai-Wu Shi

Yan Cao

Affiliations

Soon will be listed here.

Abstract

Objectives: 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 (<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (<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 CD45CD3CD43SSC neutrophils in bone marrow (<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 and a significant increase in the abundance of - (<0.05), which replaced 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 -.

References

Huang K, Mukherjee S, DesMarais V, Albanese J, Rafti E, Draghi Ii A . Targeting the PXR-TLR4 signaling pathway to reduce intestinal inflammation in an experimental model of necrotizing enterocolitis. Pediatr Res. 2018; 83(5):1031-1040. PMC: 5959752. DOI: 10.1038/pr.2018.14. View

Ratajczak M, Kucia M . Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship. Leukemia. 2021; 36(1):23-32. PMC: 8727304. DOI: 10.1038/s41375-021-01482-0. View

Song J, Dong H, Xu F, Wang Y, Li W, Jue Z . The association of severe anemia, red blood cell transfusion and necrotizing enterocolitis in neonates. PLoS One. 2021; 16(7):e0254810. PMC: 8291682. DOI: 10.1371/journal.pone.0254810. View

Wang Y, Song J, Sun H, Xu F, Li K, Nie C . Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial. J Transl Med. 2020; 18(1):308. PMC: 7414749. DOI: 10.1186/s12967-020-02459-w. View

Hutter Jr J, Hathaway W, Wayne E . Hematologic abnormalities in severe neonatal necrotizing enterocolitis. J Pediatr. 1976; 88(6):1026-31. DOI: 10.1016/s0022-3476(76)81069-4. View

Takizawa H, Fritsch K, Kovtonyuk L, Saito Y, Yakkala C, Jacobs K . Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness. Cell Stem Cell. 2017; 21(2):225-240.e5. DOI: 10.1016/j.stem.2017.06.013. View

Ragazzi S, Pierro A, Peters M, Fasoli L, Eaton S . Early full blood count and severity of disease in neonates with necrotizing enterocolitis. Pediatr Surg Int. 2003; 19(5):376-9. DOI: 10.1007/s00383-003-1014-5. View

Neu J . Necrotizing Enterocolitis: The Future. Neonatology. 2020; 117(2):240-244. DOI: 10.1159/000506866. View

Lewis K, Yoshimoto M, Takebe T . Fetal liver hematopoiesis: from development to delivery. Stem Cell Res Ther. 2021; 12(1):139. PMC: 7890853. DOI: 10.1186/s13287-021-02189-w. View

10.

Kling P, Hutter J . Hematologic abnormalities in severe neonatal necrotizing enterocolitis: 25 years later. J Perinatol. 2003; 23(7):523-30. DOI: 10.1038/sj.jp.7210983. View

11.

Hidalgo A, Libby P, Soehnlein O, Aramburu I, Papayannopoulos V, Silvestre-Roig C . Neutrophil extracellular traps: from physiology to pathology. Cardiovasc Res. 2021; 118(13):2737-2753. PMC: 9586562. DOI: 10.1093/cvr/cvab329. View

12.

Espinoza J, Kotecha R, Nakao S . Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes. Front Immunol. 2017; 8:186. PMC: 5323400. DOI: 10.3389/fimmu.2017.00186. View

13.

Chelakkot C, Ghim J, Ryu S . Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med. 2018; 50(8):1-9. PMC: 6095905. DOI: 10.1038/s12276-018-0126-x. View

14.

Yan H, Baldridge M, King K . Hematopoiesis and the bacterial microbiome. Blood. 2018; 132(6):559-564. PMC: 6085989. DOI: 10.1182/blood-2018-02-832519. View

15.

Kumar B, Connors T, Farber D . Human T Cell Development, Localization, and Function throughout Life. Immunity. 2018; 48(2):202-213. PMC: 5826622. DOI: 10.1016/j.immuni.2018.01.007. View

16.

Yan X, Cao Y, Chen W, Yu Q, Chen Y, Yao S . Peptide YVEEL protects against necrotizing enterocolitis through inhibition of toll-like receptor 4-mediated signaling in a phosphatidylinositol 3-kinase/AKT dependent manner. Front Nutr. 2022; 9:992145. PMC: 9590307. DOI: 10.3389/fnut.2022.992145. View

17.

Bazacliu C, Neu J . Necrotizing Enterocolitis: Long Term Complications. Curr Pediatr Rev. 2019; 15(2):115-124. DOI: 10.2174/1573396315666190312093119. View

18.

Moschino L, Duci M, Fascetti Leon F, Bonadies L, Priante E, Baraldi E . Optimizing Nutritional Strategies to Prevent Necrotizing Enterocolitis and Growth Failure after Bowel Resection. Nutrients. 2021; 13(2). PMC: 7910892. DOI: 10.3390/nu13020340. View

19.

Haas S, Trumpp A, Milsom M . Causes and Consequences of Hematopoietic Stem Cell Heterogeneity. Cell Stem Cell. 2018; 22(5):627-638. DOI: 10.1016/j.stem.2018.04.003. View

20.

Wu H, Guo K, Zhuo Z, Zeng R, Luo Y, Yang Q . Current therapy option for necrotizing enterocolitis: Practicalities and challenge. Front Pediatr. 2022; 10:954735. PMC: 9366471. DOI: 10.3389/fped.2022.954735. View