Gut barrier dysfunction and microbial translocation in cancer cachexia

Abstract

Purpose of ReviewCachexia is a complex metabolic syndrome characterized by skeletal muscle and adipose tissue loss and is frequently associated with emaciation, anorexia, systemic inflammation, and metabolic dysfunction. Lack of a clear understanding of the cause of cancer cachexia has impeded progress in identifying effective therapeutic agents. This review summarizes recent publications on the role of gut barrier function, intestinal microbiota, and inflammation in the etiology of cancer cachexia and new therapeutic interventions that may benefit treatment strategies.Recent FindingsSignificant advances have been made in understanding the composition and metabolic capabilities of the intestinal microbiota and its impact on gut barrier function with implications for certain inflammatory-based diseases. Recent studies reported associations between intestinal permeability and endotoxemia with development of cancer cachexia and other metabolic disorders. Improvements in intestinal function and weight gain along with decreased inflammation have been reported for potential therapeutic agents such as eicosapentaenoic acid, immunoglobulin isolates, and probiotics.SummaryContinued progress in the scientific understanding of the complex interplay between the intestinal microbiota, gut barrier function, and host inflammatory responses will uncover new therapeutic targets to help avoid the serious metabolic alterations associated with cachexia.

Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic Melanoma

“…PAF-R are mainly expressed by mesenchymal cells, which may explain the implication of adipose, muscle, liver, and heart tissue, as well as gut barrier and brain dysfunctions in cachexia, supporting our proposed model (31,32,(62)(63)(64). Also, the described crosstalk between wasting of fat tissue and skeletal muscle is compatible with the proposed mechanism (65)(66)(67).…”

The vaginal and gastrointestinal microbiomes in gynecologic cancers: A review of applications in etiology, symptoms and treatment

“…One of these articles described a possible mechanism by which cancer-related cachexia and the GI microbiome are related [58]. This report suggested that cachexia in cancer patients is due to increased intestinal permeability secondary to microbial pathogens and/or intestinal inflammation [58]. As discussed above, chemotherapy can result in increased intestinal permeability, resulting in microbial translocation of gut microbes out of the intestine, which then triggers a systemic immune response [58].…”

“…A PubMed search for "microbiome and cachexia" yielded 5 results, two of which were relevant for this review. One of these articles described a possible mechanism by which cancer-related cachexia and the GI microbiome are related [58]. This report suggested that cachexia in cancer patients is due to increased intestinal permeability secondary to microbial pathogens and/or intestinal inflammation [58].…”

Mechanisms of metabolic dysfunction in cancer-associated cachexia

“…Interestingly, colonization of the intestine by different strains of bacteria has been shown to modulate disease severity and cachexia development in mouse models (Schieber et al 2015). A role for therapeutic agents targeting intestinal function in CAC remains largely speculative at present (Klein et al 2013). Whether inhibition of browning may indirectly affect tumor metabolism is not known.…”