Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummary
Necrotizing enterocolitis (NEC) remains the leading cause of death from gastrointestinal disease in premature infants and attacks the most fragile patients at a time when they appear to be the most stable. Despite significant advances in our overall care of the premature infant, NEC mortality remain...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X18300547 |
| _version_ | 1818989208360976384 |
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| author | David J. Hackam Chhinder P. Sodhi |
| author_facet | David J. Hackam Chhinder P. Sodhi |
| author_sort | David J. Hackam |
| collection | DOAJ |
| description | Necrotizing enterocolitis (NEC) remains the leading cause of death from gastrointestinal disease in premature infants and attacks the most fragile patients at a time when they appear to be the most stable. Despite significant advances in our overall care of the premature infant, NEC mortality remains stubbornly high. There is no specific treatment for NEC beyond broad-spectrum antibiotics and intestinal resection, and current efforts have focused on preventive strategies. Over the past decade, we have proposed a unifying hypothesis to explain the pathogenesis of NEC in premature infants that suggests that NEC develops in response to an imbalance between exaggerated proinflammatory signaling in the mucosa of the premature gut leading to mucosal injury, which is not countered effectively by endogenous repair processes, and in the setting of impaired mesenteric perfusion leads to intestinal ischemia and disease development. One of the most important pathways that mediates the balance between injury and repair in the premature intestine, and that plays a key role in NEC pathogenesis, is Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide on gram-negative bacteria. This review focuses on the role that the TLR4-mediated imbalance between proinflammatory and anti-inflammatory signaling in the premature intestinal epithelium leads to the development of NEC, and will explore how an understanding of the role of TLR4 in NEC pathogenesis has led to the identification of novel preventive or treatment approaches for this devastating disease. Keywords: lneonate, Sepsis, Nutrition, Enterocyte, Microbiome, Probiotic |
| first_indexed | 2024-12-20T19:34:49Z |
| format | Article |
| id | doaj.art-259b90d2ad7d4938a89390a0520b37bf |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-20T19:34:49Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-259b90d2ad7d4938a89390a0520b37bf2022-12-21T19:28:41ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2018-01-0162229238.e1Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummaryDavid J. Hackam0Chhinder P. Sodhi1Division of General Pediatric Surgery, Johns Hopkins University, Johns Hopkins Hospital, Baltimore, Maryland; Johns Hopkins Children’s Center, Johns Hopkins Hospital, Baltimore, Maryland; Correspondence Address correspondence to: David J. Hackam, MD, Johns Hopkins Children's Center, Johns Hopkins University, Room 7323, 1800 Orleans Street, Baltimore, Maryland 21287. fax: (410) 502-5314.Division of General Pediatric Surgery, Johns Hopkins University, Johns Hopkins Hospital, Baltimore, Maryland; Johns Hopkins Children’s Center, Johns Hopkins Hospital, Baltimore, MarylandNecrotizing enterocolitis (NEC) remains the leading cause of death from gastrointestinal disease in premature infants and attacks the most fragile patients at a time when they appear to be the most stable. Despite significant advances in our overall care of the premature infant, NEC mortality remains stubbornly high. There is no specific treatment for NEC beyond broad-spectrum antibiotics and intestinal resection, and current efforts have focused on preventive strategies. Over the past decade, we have proposed a unifying hypothesis to explain the pathogenesis of NEC in premature infants that suggests that NEC develops in response to an imbalance between exaggerated proinflammatory signaling in the mucosa of the premature gut leading to mucosal injury, which is not countered effectively by endogenous repair processes, and in the setting of impaired mesenteric perfusion leads to intestinal ischemia and disease development. One of the most important pathways that mediates the balance between injury and repair in the premature intestine, and that plays a key role in NEC pathogenesis, is Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide on gram-negative bacteria. This review focuses on the role that the TLR4-mediated imbalance between proinflammatory and anti-inflammatory signaling in the premature intestinal epithelium leads to the development of NEC, and will explore how an understanding of the role of TLR4 in NEC pathogenesis has led to the identification of novel preventive or treatment approaches for this devastating disease. Keywords: lneonate, Sepsis, Nutrition, Enterocyte, Microbiome, Probiotichttp://www.sciencedirect.com/science/article/pii/S2352345X18300547 |
| spellingShingle | David J. Hackam Chhinder P. Sodhi Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummary Cellular and Molecular Gastroenterology and Hepatology |
| title | Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummary |
| title_full | Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummary |
| title_fullStr | Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummary |
| title_full_unstemmed | Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummary |
| title_short | Toll-Like Receptor–Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing EnterocolitisSummary |
| title_sort | toll like receptor mediated intestinal inflammatory imbalance in the pathogenesis of necrotizing enterocolitissummary |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X18300547 |
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