Monitor Gut Health in Children Undergoing Treatment for Acute Myeloid Leukaemia Treatment: Case-control Study

Acute myeloid leukaemia (AML) is an aggressive cancer that occurs due to the clonal expansion of immature white blood cells, known as blasts (Chaudhury et al., 2018) with generally poor outcomes compared to childhood lymphoid leukaemia (Arad-Cohen et al., 2022). While complete remission rates are high in paediatric AML at approximately 90%, event-free survival and overall survival remain suboptimal at 45% and 65%, respectively, at 3 years, and nearly half of children will relapse (Rasche et al., 2018). Recently there has been a shift towards antigen-targeting immunotherapy in the treatment of cancers, including AML, to trigger anti-leukaemic responses (Greiner, 2019).

Intestinal mucositis is one of the most common side effects of chemotherapy, resulting from disruption of the immunological balance of the intestinal mucosal barrier (De Pietri et al., 2020). This results in alterations of absorptive and secretory functions of the intestinal mucosa, haemorrhages, intestinal dysmotility or intestinal failure (McGrath, 2019; Ohta et al., 2003). Chemotherapy-induced intestinal mucositis is thought to play a central role in the development of systemic inflammation and infections (van der Velden et al., 2014). The clinical assessment of the severity of intestinal mucositis is challenged by the lack of validated scoring scales, and objective biomarkers related to mucositis pathogenesis for assessment of its severity are therefore in demand. Decreasing plasma citrulline levels have been associated with the severity of intestinal mucositis and systemic inflammation after haematopoietic stem-cell transplantation in both adults and children (Gosselin et al., 2014; van Vliet et al., 2009).

Chemotherapy-induced intestinal mucositis causes translocation of intestinal bacteria and allows bacteria to cross the damaged mucosal barrier leading to a systemic inflammation and potentially to systemic infections, especially in immunocompromised patients (Villa and Sonis, 2015). Diseases affecting the immune system, such as inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and acute leukaemia, are pathological conditions affecting the paediatric population and are often associated with alterations in the intestinal microbiota, such as a decrease in bacterial diversity (Lucafò et al., 2020). Growing evidence suggests that gut microbiota can interfere with chemotherapeutic and immunosuppressant drugs, used in the treatment of these diseases, reducing or facilitating drug efficacy (Peppas et al., 2023). Human intestinal microbiota consists of several hundred bacterial species [(Marchesi et al., 2016)]. The microbial community of the gut conveys significant benefits to human physiology at an intestinal epithelial and systematic inflammatory level [(Kindon et al., 2007; McDonnell et al., 2021) (Feng et al., 2022)].

Feeding strategies in clinical practice in paediatric cancer patients with chemotherapy-induced mucositis varies considerable but invariably requires gut rest and may require parenteral (intravenous) nutrition (Kuiken et al., 2017b)(Kuiken et al., 2017b). Parenteral nutrition is associated with significant adverse effects, namely liver injury, risk of infections, metabolic derangements, gut atrophy, dysbiosis of the intestinal microbiome (Tume et al., 2020) The gut microbiota is the most abundant type of antigen-presenting cells. Therefore, it is conceivable that parenteral nutrition may profoundly alter the gut microbiome composition and function, which could lead to detrimental effects on the intestine (Pierre, 2017).

The catastrophic impact of a fibre-devoid diet on the gut microbial recolonisation post critical illness has been described by Tanes et al,2021, the team outline the importance of introducing the right nutrition after a bout of illness (Tanes et al., 2021). The diversity and relative abundance of microbial metabolites are heavily dependent on specific dietary components [(Morrison and Preston, 2016)]. Non-digestible dietary fiber such as oligosaccharides and inulin demonstrate resistance to digestion in the human small intestine [(Lattimer and Haub, 2010)]. In the large bowel dietary fiber undergoes fermentation by colonic microbiota to produce short chain fatty acids (SCFA); acetate, butyrate and propionate, which act as the primary carbon energy source for colonocyte [5]. The synergistic relationship between the host and intestinal SCFA concentrations include the concomitant reduction of the luminal pH, which by itself inhibits pathogenic microorganisms and increases the absorption of some nutrients [(Macfarlane and Macfarlane, 2012)]. Furthermore, intestinal SCFA control the production of T-helper cells, antibodies, and cytokines and are also involved in maintaining homeostasis of the mucosal system [(Ríos-Covián et al., 2016; Corrêa-Oliveira et al., 2016)].