Gut microbiota community and metabolic profiles in direct total cavopulmonary connection and Fontan circulation: A cross-sectional study in single center

Kaiyu Wang ¹ Linjiang Han ¹ Jianrui Ma ¹ Yushen Fang ² Yinru He ¹ Xiaobing Liu ¹ WEN SHUSHENG ¹ Jian Zhuang ^1* Yuan Haiyun ^1*

• ¹ Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
• ² The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China

Background: This study aims to evaluate the direct total cavopulmonary connection (dTCPC) procedure standing on gut microbiome and metabolome as well as elucidate the gut microbiota community and metabolic profiles feature in Fontan circulation.Methods: We randomly recruited 45 participants above 14 years old undergoing Fontan operation by typical extracardiac conduit (TCPC group, n=15), direct total cavopulmonary connection (dTCPC group, n=16) procedure and healthy control (control group, n=14) in our institution between May 2023 and October 2023. 16S rRNA amplicon sequencing and untargeted metabolites measurement were performed on their fecal sample.Results: The four alpha diversity indices had no statistical significance between the dTCPC and TCPC groups (p>0.05). OPLS-DA analysis followed by permutation test showed that the model had overfitting effect between the dTCPC and TCPC groups.We observed significant differences in the Chao1 index (P=0.0236), ACE index (P=0.0236) and the unweighted beta diversity (P=0.0099) between Fontan and healthy control. Strains of Fusobacterium were significantly overrepresented (LDA scores (log10)>3) in Fontan group. Functional enrichment analysis revealed significant overrepresentation of several metabolic pathways. These predominantly included amino acid metabolism pathways such as histidine metabolism, glycine, serine and threonine metabolism as well as cysteine and methionine metabolism. Additionally, the 3 biosynthesis of unsaturated fatty acids pathway was also notably enriched.The dTCPC procedure demonstrated comparable gut microbiota composition and metabolic profiles to the traditional ECC procedure in Fontan patients.Notably, increased abundance of Fusobacterium, reduced microbial biodiversity, and altered metabolic profiles of amino acids and unsaturated fatty acids in the alimentary canal may serve as distinctive characteristics of patients who have undergone Fontan circulation. These findings provide valuable insights into the long-term physiological consequences of Fontan procedures and may inform future clinical management strategies.