Weiss 2021 Crit Care Explor
| Weiss SL, Bittinger K, Lee JJ, Friedman ES, Mattei LM, Graham K, Zhang D, Bush J, Balamuth F, McGowan FX Jr, Bushman FD, Baldassano RN, Wu GD, Wallace DC, Collman RG (2021) Decreased intestinal microbiome diversity in pediatric sepsis: a conceptual framework for intestinal dysbiosis to influence immunometabolic function. Crit Care Explor 3:0360. |
Weiss Scott L, Bittinger Kyle, Lee Jung-Jin, Friedman Elliot S, Mattei Lisa M, Graham Kathryn, Zhang Donglan, Bush Jeny, Balamuth Fran, McGowan Francis X Jr, Bushman Frederic D, Baldassano Robert N, Wu Gary D, Wallace Douglas C, Collman Ronald G (2021) Crit Care Explor
Abstract: The intestinal microbiome can modulate immune function through production of microbial-derived short-chain fatty acids. We explored whether intestinal dysbiosis in children with sepsis leads to changes in microbial-derived short-chain fatty acids in plasma and stool that are associated with immunometabolic dysfunction in peripheral blood mononuclear cells.
The design was a prospective observational pilot study with single academic PICU and forty-three children with sepsis/septic shock and 44 healthy controls.
Stool and plasma samples were serially collected for sepsis patients; stool was collected once for controls. The intestinal microbiome was assessed using 16S ribosomal RNA sequencing and alpha- and beta-diversity were determined. We measured short-chain fatty acids using liquid chromatography, peripheral blood mononuclear cell mitochondrial respiration using high-resolution respirometry, and immune function using ex vivo lipopolysaccharide-stimulated whole blood tumor necrosis factor-ฮฑ. Sepsis patients exhibited reduced microbial diversity compared with healthy controls, with lower alpha- and beta-diversity. Reduced microbial diversity among sepsis patients (mainly from lower abundance of commensal obligate anaerobes) was associated with increased acetic and propionic acid and decreased butyric, isobutyric, and caproic acid. Decreased levels of plasma butyric acid were further associated with lower peripheral blood mononuclear cell mitochondrial respiration, which in turn, was associated with lower lipopolysaccharide-stimulated tumor necrosis factor-ฮฑ. However, neither intestinal dysbiosis nor specific patterns of short-chain fatty acids were associated with lipopolysaccharide-stimulated tumor necrosis factor-ฮฑ.
Intestinal dysbiosis was associated with altered short-chain fatty acid metabolites in children with sepsis, but these findings were not linked directly to mitochondrial or immunologic changes. More detailed mechanistic studies are needed to test the role of microbial-derived short-chain fatty acids in the progression of sepsis. โข Keywords: Child, Dysbiosis, Microbiome, Mitochondria, Sepsis, Short-chain fatty acid โข Bioblast editor: Reiswig R โข O2k-Network Lab: US PA Philadelphia Wallace DC
Labels: MiParea: Respiration, Patients
Pathology: Sepsis
Organism: Human Tissue;cell: Lymphocyte Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET
Pathway: ROX
HRR: Oxygraph-2k
2021-07, PBMCs
