Abstract
Cachexia (CC) is a devastating metabolic syndrome associated with a series of underlying diseases that greatly affects life quality and expectancy among cancer patients. Studies involving mouse models, in which CC was induced through inoculation with tumor cells, originally suggested the existence of a direct correlation between the development of this syndrome and changes in the relative proportions of several bacterial groups present in the digestive tract. However, these analyses have focus solely on the characterization of bacterial dysbiosis, ignoring the possible existence of changes in the relative populations of fungi, during the development of CC. Thus, the present study sought to expand such analyses, by characterizing changes that occur in the gut fungal population (mycobiota) of mice, during the development of cancer-induced cachexia. Our results confirm that cachectic animals, submitted to Lewis lung carcinoma (LLC) transplantation, display significant differences in their gut mycobiota, when compared to healthy controls. Moreover, identification of dysbiotic fungi showed remarkable consistency across successive levels of taxonomic hierarchy. Many of these fungi have also been associated with dysbioses observed in a series of gut inflammatory diseases, such as obesity, colorectal cancer (CRC), myalgic encephalomyelitis (ME) and inflammatory bowel disease (IBD). Nonetheless, the dysbiosis verified in the LLC model of cancer cachexia seems to be unique, presenting features observed in both obesity (reduced proportion of Mucoromycota) and CRC/ME/IBD (increased proportions of Sordariomycetes, Saccharomycetaceae and Malassezia). One species of Mucoromycota (Rhyzopus oryzae) stands out as a promising probiotic candidate in adjuvant therapies, aimed at treating and/or preventing the development of CC.
Highlights
Cachexia (CC) is recognized as a metabolic syndrome associated with several underlying diseases, such as cancer, chronic kidney disease, and chronic heart disease, among others [1]
Cultivated fecal material from cachectic mice in selective coliform media, identifying Klebsiella oxytoca as the main representative of Enterobacteriaceae present in stool samples obtained from these animals. Additional studies led these authors to suggest that K. oxytoca could represent an intestinal pathobiont, capable of affecting both thickness and permeability of the mucus barrier that protects the digestive epithelium of mice, when over-represented in their gastrointestinal tract [9]. These findings demonstrated that gut dysbiosis could be an important factor for the development of cancer-induced cachexia and suggested that the control of gut microbiota composition, through the use of specific antibiotics, prebiotics and probiotics could be used as an adjuvant approach to treat and/or prevent the development of cachexia
The results described indicate that fungal gut dysbiosis is observed in a mouse model of cachexia, based on inoculation with Lewis lung carcinoma (LLC) cells
Summary
Cachexia (CC) is recognized as a metabolic syndrome associated with several underlying diseases, such as cancer, chronic kidney disease, and chronic heart disease, among others [1]. It is characterized by the reduction of muscle mass, depletion of body fat and generalized chronic inflammation [1]. J. Fungi 2020, 6, 364 life quality and expectancy, being an important cause of morbidity/mortality in more than 80% of advanced cancer cases and accounting for more than 20% of deaths [2]. Enteral or para-enteral administration of nutritional supplements is not sufficient to reverse cachexia symptoms, refuting the hypothesis that nutrient deficiency is the main causative agent of this syndrome.
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