Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Intestinal microbiome and chemotherapy-induced neutropenia (#161)

Michael Thomsen 1 , Luis Vitetta 1 , Stephen Clarke 2 3
  1. Department of Pharmacology, Sydney Medical School, Sydney, NSW, Australia
  2. Northern Clinical School, Kolling Institute of Medical Research, Sydney, NSW, Australia
  3. Department of Medicine, Sydney Medical School, Sydney, NSW, Australia

Mucositis, a painful inflammation and ulceration of mucous membranes of the intestines, is a common and therapy-limiting effect of cancer treatments. Neutropenia can interrupt treatment and may be life-threatening due to increased risk of infections with antimicrobial-resistant bacteria.

Treatment-induced disruption of intestinal mucosal barriers is associated with the release of inflammatory cytokines, further damaging tissues and progressing the systemic invasion of pathogenic bacteria: leading to febrile neutropenia. This injury induces dendritic cell/macrophage activation, uncontrolled inflammation and microbiome dysbiosis. The release of interleukins and systemic endotoxins including LPS, may be responsible for fever seen during neutropenia.1

Substituting carbapenems with antibiotic cycling for neutropenic fever has demonstrated decreased risk of vancomycin-resistant Enterococcus colonisation and reduced length of hospitalisation and duration of severe neutropenia.2  Carbapenem administration was associated with reversal of Firmicutes/Bacteroidetes phyla ratios and increases in the Bacteroides genus.  Key species including Blautia spp were also reduced, suggesting that carbapenem further disrupts the intestinal microbiome.

Modulation of the intestinal microbiota by administration of probiotics and prebiotics may influence the cross-talk between the mucosal immune system and the intestinal commensal bacteria preventing the progression of mucositis/diarrhoea that precedes increased intestinal permeability and febrile neutropenia. Probiotics, whilst not a panacea, may inhibit overgrowth of intestinal pathobionts and assist in controlling the production of mucosal immune tissue inflammatory cytokines, increase transepithelial resistance and reduce bacterial translocations.

The efficacy of the prophylactic administration of probiotics, zinc and other compounds to reduce side effects of cancer treatments such as diarrhoea, has been investigated in clinical trials with contentious results.3,4  Probiotics to reduce the risk of mucositis / febrile neutropenia remains a plausible investigational challenge. A narrative review of the clinical literature will be discussed relative to the plausible safe and tolerable administration of probiotics and prebiotics in the prevention of chemo-radiotherapy-induced intestinal commensal microbiome dysbiosis and mucositis/neutropenia.

  1. Thomsen M, Clarke S, Vitetta L. The role of adjuvant probiotics to attenuate intestinal inflammatory responses due to cancer treatments. Benef Microbes. 2018:1-18.
  2. Ford CD, Coombs J, Stofer MG, et al. Decrease in vancomycin-resistant Enterococcus colonization associated with a reduction in carbapenem use as empiric therapy for febrile neutropenia in patients with acute leukemia. Infection control and hospital epidemiology. 2019;40(7):774-779.
  3. Thomsen M, Vitetta L. Adjunctive Treatments for the Prevention of Chemotherapy- and Radiotherapy-Induced Mucositis. Integrative cancer therapies. 2018:1534735418794885.
  4. Thomsen M, Vitetta L. Zinc deficits, mucositis, and mucosal macrophage perturbation: is there a relationship? Current opinion in clinical nutrition and metabolic care. 2019;22(5):365-370.