The Gut Microbiota Predispose to the Pathophysiology of Acute Postradiotherapy Diarrhea

Manichanh, Chaysavanh; Varela, Encarna; Martínez, Cristina; Antolı́n, Maria; Llopis, Marta; Doré, Joël; Giralt, Jordi; Guarner, Francisco; Malagelada, J.-R.

doi:10.1111/j.1572-0241.2008.01868.x

Cited by 154 publications

(151 citation statements)

References 25 publications

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“…More recent studies report alterations to the microbiota after low LET X ray exposure (5–22 Gy), and observed distinct differences based on dose, amount of time following exposure, as well as presence of clinical signs such as radiation-induced diarrhea [14, 50]. One small pilot study used denaturing gradient gel electrophoresis (DGGE) to identify changes in the bacterial diversity of patients suffering from acute post-radiotherapy diarrhea (exposures to 4.3–5.4 Gy) [14].…”

Section: Discussionmentioning

confidence: 99%

Space Environmental Factor Impacts upon Murine Colon Microbiota and Mucosal Homeostasis

et al. 2015

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Astronaut intestinal health may be impacted by microgravity, radiation, and diet. The aim of this study was to characterize how high and low linear energy transfer (LET) radiation, microgravity, and elevated dietary iron affect colon microbiota (determined by 16S rDNA pyrosequencing) and colon function. Three independent experiments were conducted to achieve these goals: 1) fractionated low LET γ radiation (137Cs, 3 Gy, RAD), high Fe diet (IRON) (650 mg/kg diet), and a combination of low LET γ radiation and high Fe diet (IRON+RAD) in male Sprague-Dawley rats; 2) high LET 38Si particle exposure (0.050 Gy), 1/6 G partial weight bearing (PWB), and a combination of high LET38Si particle exposure and PWB in female BalbC/ByJ mice; and 3) 13 d spaceflight in female C57BL/6 mice. Low LET radiation, IRON and spaceflight increased Bacteroidetes and decreased Firmicutes. RAD and IRON+RAD increased Lactobacillales and lowered Clostridiales compared to the control (CON) and IRON treatments. Low LET radiation, IRON, and spaceflight did not significantly affect diversity or richness, or elevate pathogenic genera. Spaceflight increased Clostridiales and decreased Lactobacillales, and similar trends were observed in the experiment using a ground-based model of microgravity, suggesting altered gravity may affect colonic microbiota. Although we noted no differences in colon epithelial injury or inflammation, spaceflight elevated TGFβ gene expression. Microbiota and mucosal characterization in these models is a first step in understanding the impact of the space environment on intestinal health.

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Section: Discussionmentioning

confidence: 99%

Space Environmental Factor Impacts upon Murine Colon Microbiota and Mucosal Homeostasis

et al. 2015

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“…In support of such a possibility, a shift in gut microbiota composition following radiotherapy was previously shown in mouse models of segmental small bowel radiation12 and graft versus host disease (GVHD),13 14 and in human pathologies consisting of acute postradiotherapy diarrhoea,15 GVHD14 and postradiation patients with gynaecological cancer 16 17. However, hitherto, no causal effect was attributed to radiation-induced dysbiosis.…”

Section: Introductionmentioning

confidence: 89%

Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction

Gerassy-Vainberg

Blatt

Danin‐Poleg

et al. 2017

Gut

225

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Objective Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. Design We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1β correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice. Results A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology.

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“…Clinical studies of SCT recipients have also shown that the use of ciprofloxacin and metronidazole markedly reduced the incidence and severity of GVHD (Beelen et al, 1999). More recently, the role of the microbiota has also been shown of importance in MBI outside the setting of allogeneic SCT (Manichanh et al, 2008).…”

Section: Pathogenesis Of Mbi and Related Fevermentioning

confidence: 99%

“…Hence, we now know that there are three different enterotypes (Arumugam et al, 2011) and that dysbiosis has important impact on auto-immunity, allergy and auto-inflammatory diseases. There are also strong indications that the microbiota varies amongst patients with cancer and has an impact on the occurrence of MBI and the related inflammatory response (Manichanh et al, 2008;Jenq et al, 2012). Moreover, oral and colonization with Candida species have been related to the occurrence of GVHD, especially of the gut (van der Velden et al, 2013).…”

Section: Risk Prediction and Individualized Risk?mentioning

confidence: 99%

Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis

et al. 2014

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SummaryInfection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entr ee for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated hostmicrobe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapyinduced tissue damage in order to reduce fever in neutropenic patients with cancer.

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The Gut Microbiota Predispose to the Pathophysiology of Acute Postradiotherapy Diarrhea

Abstract: In this set of patients, susceptibility or protection against diarrhea after radiotherapy could be linked to different initial microbial colonization.

Cited by 154 publications

References 25 publications

Space Environmental Factor Impacts upon Murine Colon Microbiota and Mucosal Homeostasis

Space Environmental Factor Impacts upon Murine Colon Microbiota and Mucosal Homeostasis

Radiation induces proinflammatory dysbiosis: transmission of inflammatory susceptibility by host cytokine induction

Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis

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