探讨避免性/限制性食物摄入障碍(ARFID)患儿肠道菌群分布及其功能。共有135名儿童参加了这项研究,包括102名ARFID儿童和33名健康儿童。通过16SrDNA和宏基因组测序分析粪便样品以探索ARFID和健康对照(HC)组之间的肠道微生物群组成和多样性以及功能差异。ARFID患儿的肠道菌群组成和多样性与健康儿童不同,但3-6岁和7-12岁儿童的肠道菌群组成和多样性没有差异。在门一级,通过16SrDNA和宏基因组测序鉴定的两组中最丰富的微生物是相同的。在属一级,ARFID组的拟杆菌丰度较高(P>0.05);与16SrDNA测序的结果不同,宏基因组测序结果显示,ARFID组的拟杆菌丰度明显高于HC组(P=0.041)。在物种层面,大肠杆菌,嗜热链球菌和Lachnospiaelogens是ARFID组中最丰富的分类群,和Prevotellacopri,假双歧杆菌,HC组中微生物类群的前3位是gnavus和Ruminococus;两组中这些微生物类群的丰度无统计学差异。LefSe分析表明肠杆菌及其相应的肠杆菌科的丰度更高,拟杆菌科和相应的拟杆菌属,ARFID组中的类杆菌,虽然放线菌门及其相应的放线菌种类丰富,双歧杆菌和相应的双歧杆菌科,HC组中富含双歧杆菌属。Y1组和Y2组的Chao1、Shannon和Simpson指数差异无统计学意义(P=0.1,P=0.06,P=0.06)。在门一级,芽孢杆菌,拟杆菌,变形菌和放线菌是两组中最丰富的类群,但是这些细菌的丰度之间没有统计学差异(P=0.958,P=0.456,P=0.473,P=0.065)。在属一级,Y2组的粪杆菌含量高于Y1组,差异有统计学意义(P=0.037)。KEGG成果注解,ARFID患儿与健康儿童的肠道菌群功效无显著差别;然则,基于CAZy数据库,GT26在ARFID儿童中显著富集。ARFID组中最丰富的抗生素抗性基因是vanT,tetQ,adeF,ermF基因,ARFID组大环内酯类耐药基因丰度明显高于HC组(P=0.041)。与健康儿童相比,ARFID患儿的肠道菌群和功能基因分布不同.这表明肠道菌群可能在ARFID的发病机制中起重要作用。临床试验注册:ChiCTR2300074759。
To investigate the gut microbiota distribution and its functions in children with avoidant/restrictive food intake disorder (ARFID). A total of 135 children were enrolled in the study, including 102 children with ARFID and 33 healthy children. Fecal samples were analyzed to explore differences in gut microbiota composition and diversity and functional differences between the ARFID and healthy control (HC) groups via 16S rDNA and metagenomic sequencing. The gut microbiota composition and diversity in children with ARFID were different from those in heathy children, but there is no difference in the composition and diversity of gut microbiota between children at the age of 3-6 and 7-12 with ARFID. At the phylum level, the most abundant microbes in the two groups identified by 16S rDNA and metagenomic sequencing were the same. At the genus level, the abundance of Bacteroides was higher in the ARFID group (P > 0.05); however, different from the result of 16SrDNA sequencing, metagenomic sequencing showed that the abundance of Bacteroides in the ARFID group was significantly higher than that in the HC group (P = 0.041). At the species level, Escherichia coli, Streptococcus thermophilus and Lachnospira eligens were the most abundant taxa in the ARFID group, and Prevotella copri, Bifidobacterium pseudocatenulatum, and Ruminococcus gnavus were the top three microbial taxa in the HC group; there were no statistically significant differences between the abundance of these microbial taxa in the two groups. LefSe analysis indicated a greater abundance of the order Enterobacterales and its corresponding family Enterobacteriaceae, the family Bacteroidaceae and corresponding genus Bacteroides, the species Bacteroides vulgatus in ARFID group, while the abundance of the phylum Actinobacteriota and its corresponding class Actinobacteria , the order Bifidobacteriales and corresponding family Bifidobacteriaceae, the genus Bifidobacterium were enriched in the HC group. There were no statistically significant differences in the Chao1, Shannon and Simpson indices between the Y1 and Y2 groups (P = 0.1, P = 0.06, P = 0.06). At the phylum level, Bacillota, Bacteroidota, Proteobacteria and Actinobacteriota were the most abundant taxa in both groups, but there were no statistically significant differences among the abundance of these bacteria (P = 0.958, P = 0.456, P = 0.473, P = 0.065). At the genus level, Faecalibacterium was more abundant in the Y2 group than in the Y1 group, and the difference was statistically significant (P = 0.037). The KEGG annotation results showed no significant difference in gut microbiota function between children with ARFID and healthy children; however, GT26 was significantly enriched in children with ARFID based on the CAZy database. The most abundant antibiotic resistance genes in the ARFID group were the vanT, tetQ, adeF, ermF genes, and the abundance of macrolide resistance genes in the ARFID group was significantly higher than that in the HC group (P = 0.041). Compared with healthy children, children with ARFID have a different distribution of the gut microbiota and functional genes. This indicates that the gut microbiome might play an important role in the pathogenesis of ARFID.Clinical trial registration: ChiCTR2300074759.