Severe Gut Microbiota Dysbiosis Is Associated With Poor Growth in Patients With Short Bowel Syndrome
Corresponding Author
Hannah G. Piper MD
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Hannah G. Piper, MD, Department of Surgery, University of Texas Southwestern Medical Center, 1935 Medical District Dr, Dallas, TX 75235, USA. Email: [email protected]Search for more papers by this authorDi Fan MSc
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorLaura A. Coughlin MA
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorEvi X. Ho BA
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorMargaret M. McDaniel BA
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorNandini Channabasappa MD
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorJiwoong Kim MA
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorMinsoo Kim MA
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorXiaowei Zhan PhD
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorYang Xie PhD
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorAndrew Y. Koh MD
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorCorresponding Author
Hannah G. Piper MD
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Hannah G. Piper, MD, Department of Surgery, University of Texas Southwestern Medical Center, 1935 Medical District Dr, Dallas, TX 75235, USA. Email: [email protected]Search for more papers by this authorDi Fan MSc
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorLaura A. Coughlin MA
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorEvi X. Ho BA
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorMargaret M. McDaniel BA
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorNandini Channabasappa MD
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorJiwoong Kim MA
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorMinsoo Kim MA
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorXiaowei Zhan PhD
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorYang Xie PhD
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorAndrew Y. Koh MD
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorAbstract
Background: 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. Materials and Methods: 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 χ2 tests as appropriate. Results: 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. Conclusions: 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.
Supporting Information
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