The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy‐induced gastrointestinal toxicity

Secombe, Kate R.; Coller, Janet K.; Gibson, Rachel J.; Wardill, Hannah R.; Bowen, Joanne M.

doi:10.1002/ijc.31836

Cited by 66 publications

(47 citation statements)

References 86 publications

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“…The gut microbiome and its interaction with the host's innate immune system are believed to play a key role in the development of gastrointestinal reactions caused by chemotherapy; however, comprehensive bioinformatics modeling has not been carried out (38). Furthermore, to verify the correlation between changes in intestinal microbiota and the side effects of chemotherapy, one study enrolled eight patients with non-Hodgkin's lymphoma who underwent a single course of bone marrow transplantation conditioning chemotherapy.…”

Section: Ementioning

confidence: 99%

The gut microbiome can be used to predict the gastrointestinal response and efficacy of lung cancer patients undergoing chemotherapy

Zhang¹,

Zhou²,

Xu³

et al. 2020

Ann Palliat Med

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Background: Lung cancer has the highest incidence and mortality rate of any cancer worldwide. Platinumbased combination chemotherapy is still the standard treatment for advanced lung cancer. However, the clinical efficacy of this treatment can be affected by its adverse reactions, especially gastrointestinal mucositis.The adverse reactions often lead to delayed and reduced medication. The role played by gut microbiome in the treatment of cancer is becoming clearer, and evidence suggests that regulation of the gut microbiome may affect the response to multiple types of cancer treatment.Methods: Sixty lung cancer patients who received chemotherapy for the first time and 17 healthy subjects were enrolled in this study. A metagenomic analysis of 137 fecal samples was performed using nextgeneration sequencing technology. Results:The relative abundance of Eubacterium, Ruminococcus, and Faecalibacterium was higher in the lung cancer patients than in the healthy subjects; however, the relative abundance of Prevotella, Streptococcus, Enterococcus, and Roseburia showed the opposite result. The relative abundance of each gut microbiome changed significantly during chemotherapy. At the phylum level, the relative abundance of Firmicutes and Euryarchaeota was dramatically increased after chemotherapy. Lung cancer patients with a higher relative abundance of a particular bacterial genus, such as Prevotella, Megamonas, Streptococcus, Faecalibacterium, Roseburia, Parabacteroides, Coprococcus, Oscillibacter, Dorea, or Chlamydia, at baseline were more likely to experience gastrointestinal reactions. These results show that the intestinal flora can play a role in predicting the effect of chemotherapy in lung cancer patients. Conclusions:The gut microbiome of patients with lung cancer differs from those of healthy people.The results of this study suggest that Ruminococcus and Eubacterium may be related to the occurrence and development of lung cancer. The gut microbiome of lung cancer patients changes significantly after treatment with cytotoxic drugs, which may be associated with the gastrointestinal reaction caused by chemotherapy. The gut microbiome also can be used to predict the efficacy of chemotherapy in lung cancer patients.

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Section: Ementioning

confidence: 99%

The gut microbiome can be used to predict the gastrointestinal response and efficacy of lung cancer patients undergoing chemotherapy

Zhang¹,

Zhou²,

Xu³

et al. 2020

Ann Palliat Med

View full text Add to dashboard Cite

show abstract

“…Bacterial colonization at the injured sites was documented and linked with secondary complications such as bacteremia and sepsis. Technological advances have facilitated a clearer mechanistic appreciation of the contribution of gut microbiota to GI toxicity in anti-cancer therapy [33,34], however dissecting the causative role for the microbiome in GI toxicity remains challenging. Current evidence suggests that microbial disruption observed in GI toxicity exacerbates the pathobiology of GI toxicity [34] via direct effects on drug metabolism, modulation of the host immune system and disruption of the intestinal barrier.…”

Section: Emerging Applications Of Fmt In Supportive Oncologymentioning

confidence: 99%

“…Technological advances have facilitated a clearer mechanistic appreciation of the contribution of gut microbiota to GI toxicity in anti-cancer therapy [33,34], however dissecting the causative role for the microbiome in GI toxicity remains challenging. Current evidence suggests that microbial disruption observed in GI toxicity exacerbates the pathobiology of GI toxicity [34] via direct effects on drug metabolism, modulation of the host immune system and disruption of the intestinal barrier. Furthermore, it is becoming increasingly clear that an individual's unique microbiome is critical in shaping their response to treatment [35].…”

Section: Emerging Applications Of Fmt In Supportive Oncologymentioning

confidence: 99%

Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients

et al. 2019

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FMT has gained enormous momentum in the treatment of acute inflammatory and infectious diseases. Despite an encouraging safety profile, FMT has been met with caution in the oncological setting due to perceived infectious risks in immunocompromised patients. Theoretical risks aside, the application of FMT in oncology may stand to benefit patients, via modulation of treatment efficacy and the mitigation of treatment complications. Here, we summarize most recent safety data of FMT in immunocompromised cohorts, including people with cancer, highlighting that FMT may actually provide protection against bacterial translocation via introduction of a diverse microbiome and restoration of epithelial defenses. We also discuss the emerging translational applications of FMT within supportive oncology, including the prevention and treatment of graft vs. host disease and sepsis, treatment of immunotherapy-induced colitis and restoration of the gut microbiome in survivors of childhood cancer.

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“…4,5 Despite the clear need, there remains no gold standard method to prevent MTX-induced mucositis. 6 The most recent advance in our understanding of MTX-induced mucositis has been the impact of the microbiota, 7,8 in particular the microbial composition at the time of MTX administration. Preliminary evidence from our laboratory shows that antibioticinduced disruption of the microbiota worsens MTXinduced mucositis, increasing MTX-mortality and impairing mucosal recovery.…”

Section: Introductionmentioning

confidence: 99%

Pre-therapy fasting slows epithelial turnover and modulates the microbiota but fails to mitigate methotrexate-induced gastrointestinal mucositis

et al. 2020

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Background: Recent findings by Tang et al. (2020) show dietary restriction (30%, 2 weeks) prevents methotrexate-induced mortality by modulation of the microbiota, specifically the expansion of Lactobacillus. While fundamentally insightful, upscaling this schedule is a major obstacle to clinical uptake. Here, we evaluate a safe and clinically achievable schedule of pre-therapy fasting for 48 h on microbiota composition, body composition and intestinal proliferation, and assess its impact on the severity of methotrexate-induced gastrointestinal mucositis using a validated preclinical rat model. Methods: Age-and weight-matched male Wistar rats were treated with a sublethal dose of 45 mg/ kg methotrexate with or without pre-therapy fasting. The impact of acute fasting on epithelial proliferation, body composition and the microbiota was assessed using plasma citrulline, Ki67 immunohistochemistry, miniSpec and 16S rRNA sequencing. The severity of gastrointestinal mucositis was evaluated using plasma citrulline and body weight. Results: Whilst pre-therapy fasting slowed epithelial proliferation and increased microbial diversity and richness, it also induced significant weight loss and was unable to attenuate the severity of mucositis in both age-and weight-matched groups. In contrast to Tang et al., we saw no expansion of Lactobacillus following acute fasting. Conclusions: Our findings suggest that the beneficial effects of acute fasting are masked by the detrimental effects on body weight and composition and lacking influence on Lactobacillus. Future studies should consider alternative fasting schedules or aim to induce comparable microbial and mucosal manipulation without compromising body composition using clinically feasible methods of dietary or microbial intervention.

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The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy‐induced gastrointestinal toxicity

Cited by 66 publications

References 86 publications

The gut microbiome can be used to predict the gastrointestinal response and efficacy of lung cancer patients undergoing chemotherapy

The gut microbiome can be used to predict the gastrointestinal response and efficacy of lung cancer patients undergoing chemotherapy

Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients

Pre-therapy fasting slows epithelial turnover and modulates the microbiota but fails to mitigate methotrexate-induced gastrointestinal mucositis

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