The microbiome’s relationship with congenital heart disease: more than a gut feeling

Abstract

Patients with congenital heart disease (CHD) are at risk for developing intestinal dysbiosis and intestinal epithelial barrier dysfunction due to abnormal gut perfusion or hypoxemia in the context of low cardiac output or cyanosis. Intestinal dysbiosis may contribute to systemic inflammation thereby worsening clinical outcomes in this patient population. Despite significant advances in the management and survival of patients with CHD, morbidity remains significant and questions have arisen as to the role of the microbiome in the inflammatory process. Intestinal dysbiosis and barrier dysfunction experienced in this patient population are increasingly implicated in critical illness. This review highlights possible CHD-microbiome interactions, illustrates underlying signaling mechanisms, and discusses future directions and therapeutic translation of the basic research.

Clinical Characteristics and Potential Pathogenesis of Cardiac Necrotizing Enterocolitis in Neonates with Congenital Heart Disease: A Narrative Review

“…Additional factors thought to play a role in the pathogenesis of cardiac NEC are similar to those of classical NEC. Pathogenic bacteria likely to translocate the ischemically compromised intestinal epithelium in cardiac NEC originate from an altered microbiome, similar to that of classical NEC [ 51 ], but in the case of cardiac NEC, have likely proliferated due to intestinal hypoperfusion, venous congestion and bowel wall edema, and associated inflammation [ 52 ]. Infants with cardiac NEC harbor additional Firmicutes, but reduced Actinobacteria, Bacteroidetes, and Enterobacteriaceae, as well as reduced total bacterial counts, compared with healthy controls [ 53 ].…”

“…Unfortunately, small clinical trials administering probiotics in infants undergoing CHD surgery have yet to demonstrate a reversal of this dysbiosis, nor significant benefits to the infant [ 53 , 54 ]. This enduring hypoperfusion-induced dysbiosis further weakens the intestinal barrier, allowing inflammatory molecules such as trimethylamine N-oxide (TMAO) to additionally activate the endothelium [ 52 ]. Low blood flow, in combination with the induced overgrowth of proinflammatory, facultative anaerobes spurred by this low oxygen environment, induce upregulation of hypoxia inducible factor-1 alpha (HIF-1α) and NF-κB (nuclear transcription factor-κB), the latter influenced by either a reduction in butyrate-producing organisms [ 52 ] or crosstalk with HIF-1α [ 55 ].…”

“…This enduring hypoperfusion-induced dysbiosis further weakens the intestinal barrier, allowing inflammatory molecules such as trimethylamine N-oxide (TMAO) to additionally activate the endothelium [ 52 ]. Low blood flow, in combination with the induced overgrowth of proinflammatory, facultative anaerobes spurred by this low oxygen environment, induce upregulation of hypoxia inducible factor-1 alpha (HIF-1α) and NF-κB (nuclear transcription factor-κB), the latter influenced by either a reduction in butyrate-producing organisms [ 52 ] or crosstalk with HIF-1α [ 55 ]. While both transcription factors upregulate genes with a protective role in intestinal barrier function, hypoxia-induced inflammation often results in increased intestinal permeability and cytokine production, resulting in excessive intestinal inflammation [ 56 ].…”

Human milk feeding and direct breastfeeding improve outcomes for infants with single ventricle congenital heart disease: Propensity score matched analysis of the NPC-QIC registry

“…Knowledge about the gut microbiome of infants with CHD is only beginning to emerge, [64][65][66][67][68][69] and there has been no investigation into HM composition in the context of CHD. A 2022 study by Huang et al.…”

“…64 The authors propose Bifidobacterium and oligosaccharide supplementation for infants with critical CHD, but stop short of recommending improved lactation support for these infants and their families as a mechanism to promote intestinal homeostasis. Of the remaining abstracts, 69 studies, 65,67,68 or reviews 66 identified on the topic of the gut microbiome in patients with CHD, only one briefly mentions HM/BF 68 and none discuss HM/BF as a therapeutic intervention for gut dysbiosis.…”