Tessier Mary Elizabeth M, Cavallo Laurel, Yeh Jennifer, Harpavat Sanjiv, Hoffman Kristi L, Petrosino Joseph F, Shneider Benjamin L
Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine/Texas Children's Hospital.
Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX.
J Pediatr Gastroenterol Nutr. 2020 Jun;70(6):789-795. doi: 10.1097/MPG.0000000000002686.
Biliary atresia's (BA) response to surgical Kasai portoenterostomy (KP) is uneven and dependent upon bile flow; 50% of infants require a liver transplant by 24 months. We hypothesized that the microbiome may identify and associate with outcomes in BA.
Stool samples were collected from infants with cholestasis (n = 15), 8 of which with BA were followed longitudinally.16S sequencing was performed on all samples (n = 45). Whole Genome Sequencing (WGS) was performed on BA pre-KP samples (n = 8). Infants with BA, other forms of cholestasis, BA infants with very good bile flow (VGBF) and not (nVGBF) (VGBF dichotomized by TSBA <40 μmol/L by 6 months) were compared.
Of the 8 infants with BA, 4 infants had VGBF. Microbial richness was inversely proportional to degree of cholestasis (P = 0.046). Increased Bifidobacterium abundance associated with VGBF (P = 0.03) and decreased cholestasis (P < 0.01) at 1 month post-KP. Pre-KP, community structure differed in infants with BA versus other cholestasis. Interestingly, infants who subsequently achieved VGBF had increased diversity (P = 0.03) and different community structure at the pre-KP time point. WGS corroborated Bifidobacterium's pre-KP importance.
The microbiome differs between infants with BA and other cholestasis. It additionally differs between infants with BA who have good and poor bile flow, and thus outcomes, post-KP. These differences are seen even before KP. These data suggest that bile influences the development of the infant microbiome and that there may be possible influences of the pre- and post-KP microbiome on bile flow after KP. Further larger studies are needed to confirm these findings.
胆道闭锁（BA）对手术性Kasai肝门空肠吻合术（KP）的反应参差不齐，且取决于胆汁流动情况；50%的婴儿在24个月时需要进行肝移植。我们推测微生物群可能与BA的预后相关并可用于识别。
收集了胆汁淤积婴儿的粪便样本（n = 15），其中8例BA婴儿进行了纵向随访。对所有样本（n = 45）进行16S测序。对KP术前的BA样本（n = 8）进行全基因组测序（WGS）。比较了BA婴儿、其他形式胆汁淤积的婴儿、术后胆汁流动良好（VGBF）和胆汁流动不佳（nVGBF）的BA婴儿（VGBF以6个月时总血清胆红素<40μmol/L进行二分法划分）。
8例BA婴儿中，4例婴儿胆汁流动良好。微生物丰富度与胆汁淤积程度呈负相关（P = 0.046）。术后1个月，双歧杆菌丰度增加与VGBF相关（P = 0.03），且胆汁淤积减轻（P < 0.01）。术前，BA婴儿与其他胆汁淤积婴儿的群落结构不同。有趣的是，随后实现VGBF的婴儿在KP术前时间点多样性增加（P = 0.03）且群落结构不同。WGS证实了术前双歧杆菌的重要性。
BA婴儿与其他胆汁淤积婴儿的微生物群不同。此外，KP术后胆汁流动良好和不佳的BA婴儿的微生物群也不同，因此预后也不同。这些差异在KP术前就已出现。这些数据表明胆汁会影响婴儿微生物群的发育，并且KP术前和术后的微生物群可能对KP术后的胆汁流动有影响。需要进一步开展更大规模的研究来证实这些发现。
