Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection

Frisbee, Alyse; Petri, William A.

doi:10.1016/j.molmed.2020.01.009

Cited by 26 publications

(34 citation statements)

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“…Investigations have thus far fallen into two specific pathways-first, using probiotics to help restore a premorbid microbiome, or second, to use antibiotics through an SDD approach to target specific families of organisms so as to alter the microbiome in possibly beneficial ways. Further novel pharmacologic options that have direct gut microbiome modifying effects are also under development, including faecal transplantation as a possible novel treatment for microbiota dysregulation (considering the immune system during faecal microbiota transplantation for Clostridioides difficile infection [55] and for the decolonization of antibioticresistant bacteria in the gut [56]). One of the major challenges of studying the effect of these interventions is the huge variability in the gut microbiome of critically ill patients, even during the first days of ICU admission [57].…”

Section: Gut-lung Axis and The Possible Interventionsmentioning

confidence: 99%

The importance of airway and lung microbiome in the critically ill

et al. 2020

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During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances. Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology. The body's resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity. In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.

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Section: Gut-lung Axis and The Possible Interventionsmentioning

confidence: 99%

The importance of airway and lung microbiome in the critically ill

et al. 2020

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“…[148][149][150] Then, SFB induce a proinflammatory gene program that confers protection against pathogens like Citrobacter rodentium 149 but that can also lead to inflammatory and autoimmune disorders. 142,151,152 In a very recent report, Cook et al investigated how FMT affects CDI immunity. Patients with recurrent CDI have a reduced frequency of circulating TcdB-specific CD4 + Th17 cells but not CD4 + Th1 and Th2 cells 153 (Fig.…”

Section: Fecal Microbiota Transplant (Fmt) and The Immune Responses Dmentioning

confidence: 99%

The adaptive immune response toClostridioides difficile: A tricky balance between immunoprotection and immunopathogenesis

Pino

Barbero

Español

et al. 2020

Journal of Leukocyte Biology

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Clostridioides difficile (C. difficile) is the major cause of hospital-acquired gastrointestinal infections in individuals following antibiotics treatment. The pathogenesis of C. difficile infection (CDI) is mediated mainly by the production of toxins that induce tissue damage and host inflammatory responses. While innate immunity is well characterized in human and animal models of CDI, adaptive immune responses remain poorly understood. In this review, the current understanding of adaptive immunity is summarized and its influence on pathogenesis and disease outcome is discussed. The perspectives on what we believe to be the main pending questions and the focus of future research are also provided. There is no doubt that the innate immune response provides a first line of defense to CDI. But, is the adaptive immune response a friend or a foe? Probably it depends on the course of the disease. Adaptive immunity is essential for pathogen eradication, but may also trigger uncontrolled or pathological inflammation. Most of the understanding of the role of T cells is based on findings from experimental models. While they are a very valuable tool for research studies, more studies in human are needed to translate these findings into human disease. Another main challenge is to unravel the role of the different T cell populations on protection or induction of immunopathogenesis.

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“…Given the importance of IgA in maintaining intestinal homeostasis, a better understanding of these interactions and their recovery after FMT could help improve the rational design of microbial therapies for rCDI infection. 28 This study has several limitations. The study cohort consisted of a small sample size from a single center.…”

Section: Discussionmentioning

confidence: 92%