TY - JOUR
T1 - The common prophylactic therapy for bowel surgery is ineffective for clearing Bacteroidetes, the primary inducers of systemic inflammation, and causes faster death in response to intestinal barrier damage in mice
AU - Sinsimer, Daniel
AU - Esseghir, Amira
AU - Tang, May
AU - Laouar, Amale
PY - 2014
Y1 - 2014
N2 - Introduction and objective: The role of secreted gut microbial components in the initiation of systemic inflammation and consequences of antibiotic therapies on this inflammatory process are poorly elucidated. We investigate whether peripheral innate cells mount an inflammatory response to gut microbial components, the immune cells that are the primary drivers of systemic inflammation, the bacterial populations that are predominantly responsible, and whether perioperative antibiotics affect these processes. Method and experimental design: Conditioned supernatants from gut microbes were used to stimulate murine innate cell types in vitro and in vivo, and proinflammatory responses were characterised. Effects of antibiotic therapies on these responses were investigated using a model of experimental intestinal barrier damage induced by dextran sodium sulfate. Results: Proinflammatory responses in the periphery are generated by components of anaerobes from the Bacteroidetes phylotype and these responses are primarily produced by myeloid dendritic cells. We found that the common prophylactic therapy for sepsis (oral neomycin and metronidazole administered to patients the day prior to surgery) is ineffective for clearing Bacteroidetes from the murine intestine. A point of critical consequence of this result is the increased systemic inflammation and premature death observed in treated mice, and these outcomes appear to be independent of gut bacterial spread in the initial phase of intestinal barrier damage. Importantly, spillage of gut microbial products, rather than dissemination of gut microbes, may underlay the initiation of systemic inflammation leading to death. Conclusions: Our data further affirm the importance of a balanced gut microflora biodiversity in host immune homeostasis and reinforce the notion that inadequate antibiotic therapy can have detrimental effects on overall immune system.
AB - Introduction and objective: The role of secreted gut microbial components in the initiation of systemic inflammation and consequences of antibiotic therapies on this inflammatory process are poorly elucidated. We investigate whether peripheral innate cells mount an inflammatory response to gut microbial components, the immune cells that are the primary drivers of systemic inflammation, the bacterial populations that are predominantly responsible, and whether perioperative antibiotics affect these processes. Method and experimental design: Conditioned supernatants from gut microbes were used to stimulate murine innate cell types in vitro and in vivo, and proinflammatory responses were characterised. Effects of antibiotic therapies on these responses were investigated using a model of experimental intestinal barrier damage induced by dextran sodium sulfate. Results: Proinflammatory responses in the periphery are generated by components of anaerobes from the Bacteroidetes phylotype and these responses are primarily produced by myeloid dendritic cells. We found that the common prophylactic therapy for sepsis (oral neomycin and metronidazole administered to patients the day prior to surgery) is ineffective for clearing Bacteroidetes from the murine intestine. A point of critical consequence of this result is the increased systemic inflammation and premature death observed in treated mice, and these outcomes appear to be independent of gut bacterial spread in the initial phase of intestinal barrier damage. Importantly, spillage of gut microbial products, rather than dissemination of gut microbes, may underlay the initiation of systemic inflammation leading to death. Conclusions: Our data further affirm the importance of a balanced gut microflora biodiversity in host immune homeostasis and reinforce the notion that inadequate antibiotic therapy can have detrimental effects on overall immune system.
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U2 - 10.1136/bmjgast-2014-000009
DO - 10.1136/bmjgast-2014-000009
M3 - Article
AN - SCOPUS:85046447891
SN - 2054-4774
VL - 1
JO - BMJ Open Gastroenterology
JF - BMJ Open Gastroenterology
IS - 1
M1 - e000009
ER -