title: Severe Gut Microbiota Dysbiosis Is Associated With Poor Growth in Patients With Short Bowel Syndrome.
abstract: Children with short bowel syndrome (SBS) can vary significantly in their growth trajectory. Recent data have shown that children with SBS possess a unique gut microbiota signature compared with healthy controls. We hypothesized that children with SBS and poor growth would exhibit more severe gut microbiota dysbiosis compared with those with SBS who are growing adequately, despite similar intestinal anatomy.
  
  
  
  Stool samples were collected from children with SBS (n = 8) and healthy controls (n = 3) over 3 months. Gut microbiota populations (16S ribosomal RNA sequencing and metagenomic shotgun sequencing) were compared, including a more in-depth analysis of SBS children exhibiting poor and good growth. Statistical analysis was performed using Mann-Whitney, Kruskal-Wallis, and χ2tests as appropriate.
  
  
  
  Children with SBS had a significant deficiency of the commensal Firmicutes order Clostridiales ( P = .025, Kruskal-Wallis) compared with healthy children. Furthermore, children with SBS and poor growth were deficient in beneficial bacteria known to produce short-chain fatty acids and had expansion of proinflammatory Enterobacteriaceae ( P = .038, Kruskal-Wallis) compared with children with SBS who were growing adequately. Using metabolic function analyses, SBS/poor growth microbiomes were deficient in genes needed for gluconeogenesis but enriched in branched and aromatic amino acid synthesis and citrate cycle pathway genes.
  
  
  
  Patients with SBS, particularly those with suboptimal growth, have a marked gut dysbiosis characterized by a paucity of beneficial commensal anaerobes, resulting in a deficiency of key metabolic enzymes found in the gut microbiomes of healthy children.
authors.affiliation: 1 Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Hannah G
authors.initials: HG
authors.lastname: Piper
authors.affiliation: 2 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Fan
authors.affiliation: 2 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Coughlin
authors.affiliation: 2 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Evi X
authors.initials: EX
authors.lastname: Ho
authors.affiliation: 3 Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: McDaniel
authors.affiliation: 2 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Nandini
authors.initials: N
authors.lastname: Channabasappa
authors.affiliation: 4 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|5 Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jiwoong
authors.initials: J
authors.lastname: Kim
authors.affiliation: 4 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|5 Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: 4 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|5 Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|6 Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhan
authors.affiliation: 4 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|5 Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|7 Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: 1 Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|7 Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|8 Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Koh
mesh_terms: D001419:Bacteria / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D000068016:Eubacteriales / Q000235:genetics; D064806:Dysbiosis / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D004755:Enterobacteriaceae / Q000235:genetics; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics; D006130:Growth Disorders / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000382:microbiology; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008297:Male; D012778:Short Bowel Syndrome / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D015430:Weight Gain
chemical_list: D005232:Fatty Acids, Volatile
keywords: life cycle; microbiome; pediatrics; research and diseases; short bowel syndrome