Pitfalls and novel experimental approaches to optimize microbial interventions for chemotherapy-induced gastrointestinal mucositis

Abstract

Purpose of review There is a growing number of studies implicating gut dysbiosis in mucositis development. However, few studies have shed light on the causal relationship limiting translational potential. Here, we detail the key supportive evidence for microbial involvement, candidate mechanisms by which the microbiome may contribute to mucositis and emerging approaches to model host–microbe interactions with clinical relevance and translational potential. Recent findings Synthesis of existing clinical data demonstrate that modulating the microbiome drastically alters the development and severity of mucositis, providing a strong rationale for its involvement. Review of the literature revealed potential microbiome-dependent mechanisms of mucosal injury including altered drug metabolism, bile acid synthesis and regulation of the intestinal barrier. Current studies are limited in their mechanistic insight due to cross-sectional and would benefit from longitudinal analyses and baseline phenotyping. Summary The causative role of the microbiome in mucositis development remains unclear. Future studies must adopt comprehensive microbial analyses with functional assessment, and utilize emerging ex-vivo models to interrogate host–microbe interactions in mucositis.

Antibiotic-induced disruption of the microbiome exacerbates chemotherapy-induced diarrhoea and can be mitigated with autologous faecal microbiota transplantation

“…All experiments were conducted in NZ9 rats / group repeated once. ) indicates P<0.05, )) indicates P<0.02, ))) indicates P<0.001. changes are directly mediated by chemotherapy or simply a form of collateral damage resulting from mucosal injury [27]. Our data support the latter, with FMT delivered after MTX failing to appreciably impact mucosal injury (defined by citrulline) and its clinical manifestations (weight loss and anorexia), despite maintaining a more stable microbiome composition defined by 16S sequencing.…”

Does Chemotherapy-Induced Gastrointestinal Mucositis Affect the Bioavailability and Efficacy of Anti-Infective Drugs?

“…Intestinal atrophy and consequently impaired intestinal function are well-documented phenomena during GI-M [1,42,[51][52][53]. This is supported by numerous studies showing that reduced citrulline levels (a non-essential amino acid synthesized by small bowel enterocytes and validated biomarker of GI-M) are associated with loss of enterocyte mass and consequently to a reduced mucosal surface area [54,55].…”

New Insights into the Relationship between Gut Microbiota and Radiotherapy for Cancer

“…Bile acids in the human colon can be converted into deoxycholic acid and lithotomic acid under the action of intestinal microorganisms such as Bacteroides intestinalis , Bacteroides fragilis , and E. coli . When the balance of the microbiome is disturbed, the proportion of primary/secondary bile acids increases [ 81 , 82 , 83 ]. Fang et al [ 84 ] suggested that the CPT-11-induced disturbance of bile acid metabolism may inhibit the production of IL-10, which in turn aggravates the high permeability of the mucosal barrier, while in the case of radiation enteritis, the relationship between gut microbiota, bile acid metabolism, and radiation enteritis needs further experimental research.…”