Gut microbiota and metabolic aspects of cancer cachexia

Ziemons, Janine; Smidt, Marjolein L.; Damink, Steven W. M. Olde; Rensen, Sander S.

doi:10.1016/j.beem.2021.101508

Cited by 20 publications

(23 citation statements)

References 57 publications

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“…2). In addition to the involvement of adipose tissue and the brain in the cachectic process, recent evidence suggests that the gut microbiota is involved in cancer cachexia 91,92 . In the proposed gut microbiota and skeletal muscle axis, the gut microbiota generates metabolites that are delivered to skeletal muscle, leading to increased energy expenditure in muscle cells 93,94 .…”

Section: Cancer Cachexia As a Multiorgan Syndromementioning

confidence: 99%

Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia

Yeom

2022

Exp Mol Med

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Cancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional impairment, weakness, and wasting, and it affects treatment success and quality of life. Two major symptoms of cancer cachexia are anorexia and weight loss. Weight loss in cachexia is not reversed through increased food intake, suggesting that anorexia and weight loss in cancer patients are regulated by independent molecular mechanisms. Although the wasting phenotype mostly occurs in skeletal muscle and adipose tissue, other organs, such as the brain, liver, pancreas, heart, and gut, are also involved in cachexia. Thus, cachexia is a multiorgan syndrome. Although the molecular basis of cancer cachexia-induced weight loss is known, the mechanism underlying anorexia is poorly understood. Here, we highlight our recent discovery of a new anorexia mechanism by which a tumor-derived humoral factor induces cancer anorexia by regulating feeding-related neuropeptide hormones in the brain. Furthermore, we elucidated the process through which anorexia precedes tissue wasting in cachexia. This review article aims to provide an overview of the key molecular mechanisms of anorexia and tissue wasting caused by cancer cachexia.

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Section: Cancer Cachexia As a Multiorgan Syndromementioning

confidence: 99%

Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia

Yeom

2022

Exp Mol Med

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“…More specifically, the gut microbiota has been demonstrated to modulate energy harvest from the diet, systemic inflammation, gut barrier function, and insulin sensitivity, which are metabolic features found to be altered in cancer cachexia 4,5 . In light of these findings, it is not surprising that recent animal data indicate that the gut microbiota might be involved in the pathogenesis of cancer cachexia 6,7 . For example, Bindels et al .…”

Section: Introductionmentioning

confidence: 99%

“… 4 , 5 In light of these findings, it is not surprising that recent animal data indicate that the gut microbiota might be involved in the pathogenesis of cancer cachexia. 6 , 7 For example, Bindels et al . repeatedly demonstrated that cachexia was associated with profound changes in gut microbiota composition and diversity in mouse models of leukaemia and colon cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Mechanistically, the gut microbiota has been shown to influence muscle metabolism by modulating amino acid availability and through the impact of microbial metabolites on glucose metabolism and muscle glycogen availability. 7 Important microbial metabolites exerting systemic effects are bile acids, branched‐chain fatty acids (BCFAs), and short‐chain fatty acids (SCFA), which are produced by macronutrient degradation and released into the blood. 12 The SCFA acetate, propionate, butyrate, and valerate are generated by microbial fermentation of dietary fibres and are closely linked to metabolic health.…”

Section: Introductionmentioning

confidence: 99%

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Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients

Ubachs

Ziemons

Soons

et al. 2021

J cachexia sarcopenia muscle

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Background Cancer cachexia is characterized by a negative energy balance, muscle and adipose tissue wasting, insulin resistance, and systemic inflammation. Because of its strong negative impact on prognosis and its multifactorial nature that is still not fully understood, cachexia remains an important challenge in the field of cancer treatment. Recent animal studies indicate that the gut microbiota is involved in the pathogenesis and manifestation of cancer cachexia, but human data are lacking. The present study investigates gut microbiota composition, short‐chain fatty acids (SCFA), and inflammatory parameters in human cancer cachexia. Methods Faecal samples were prospectively collected in patients (N = 107) with pancreatic cancer, lung cancer, breast cancer, or ovarian cancer. Household partners (N = 76) of the patients were included as healthy controls with similar diet and environmental conditions. Patients were classified as cachectic if they lost >5% body weight in the last 6 months. Gut microbiota composition was analysed by sequencing of the 16S rRNA V4 gene region. Faecal SCFA levels were quantified by gas chromatography. Faecal calprotectin was assessed with enzyme‐linked immunosorbent assay. Serum C‐reactive protein and leucocyte counts were retrieved from medical records. Results Cachexia prevalence was highest in pancreatic cancer (66.7%), followed by ovarian cancer (25%), lung cancer (20.8%), and breast cancer (17.3%). Microbial α‐diversity was not significantly different between cachectic cancer patients (N = 33), non‐cachectic cancer patients (N = 74), or healthy controls (N = 76) (species richness P = 0.31; Shannon effective index P = 0.46). Community structure (β‐diversity) tended to differ between these groups (P = 0.053), although overall differences were subtle and no clear clustering of samples was observed. Proteobacteria (P < 0.001), an unknown genus from the Enterobacteriaceae family (P < 0.01), and Veillonella (P < 0.001) were more abundant among cachectic cancer patients. Megamonas (P < 0.05) and Peptococcus (P < 0.001) also showed differential abundance. Faecal levels of all SCFA tended to be lower in cachectic cancer patients, but only acetate concentrations were significantly reduced (P < 0.05). Faecal calprotectin levels were positively correlated with the abundance of Peptococcus, unknown Enterobacteriaceae, and Veillonella. We also identified several correlations and interactions between clinical and microbial parameters. Conclusions This clinical study provided the first insights into the alterations of gut microbiota composition and SCFA levels that occur in cachectic cancer patients and how they are related to inflammatory parameters. These results pave the way for further research examining the role of the gut microbiota in cancer cachexia and its potential use as therapeutic target.

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“…Interventions to target the gut microbiome in cancer cachexia can largely be classified into: (1) Prebiotics, which are nondigestible substrates that can induce growth or activity of microorganisms in the host; (2) Probiotics that contain live microorganisms to be introduced to the host; and (3) Synbiotics, which are mixtures of live microorganisms and substrates utilized by the host (combination of prebiotics and probiotics)[ 17 ].…”

Section: Future Considerations For Clinical Translationmentioning

confidence: 99%

Gut microbiome and pancreatic cancer cachexia: An evolving relationship

Hendifar¹,

Akinsola²,

Muranaka³

et al. 2022

WJGO

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Nearly 80% of patients with pancreatic ductal adenocarcinoma (PDAC) develop cachexia along their disease course. Cachexia is characterized by progressive weight loss, muscle wasting, and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life. Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support, pancreatic enzyme replacement therapy, and/or pharmacologic interventions. Despite current interventions to mitigate PDAC cachexia, a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome. We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC. Additionally, we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia. Novel insights into the relationship between enteral nutritional support, cachexia, and the gut microbiome are presented. These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia.

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Gut microbiota and metabolic aspects of cancer cachexia

Cited by 20 publications

References 57 publications

Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia

Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia

Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients

Gut microbiome and pancreatic cancer cachexia: An evolving relationship

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