Potential benefits of some microbiota-targeting nutrients in cancer cachexia

I participated to the conference “Targeting Microbiota” to update my knowledge concerning the gut microbiota and to foster collaborations with other scientists in the field. It was also a great opportunity to present my ongoing work.

This congress was scientifically very fruitful. I was impressed by the quality of the invited speakers. The congress covered a broad panel of pathologies to which gut microbial dysbiosis could contribute, from liver diseases to spontaneous autoimmune demyelination. In my opinion, this congress typically exemplifies a trend of the last decade, namely that the gut microbiota is able to influence biological processes happening outside of the gastrointestinal tract, such as, for instance, adipose tissue physiology, lung immunity, placenta development and function, and social cognition. Interestingly, more and more studies are investigating the mechanisms underlying this crosstalk. We also attended a special session on fecal microbiota transplantation, where it became evident that we are far from reaching a consensus in terms of safety and broad clinical applications.

Nathalie Delzenne and Laure Bindels (UCL, Belgium)

In a short talk, I presented a recent study performed in the lab of Prof Delzenne, in collaboration with Dr Neyrinck, and investigating the potential benefits of some microbiota-targeting nutrients in a mouse model of cancer cachexia.

Cancer cachexia is a complex metabolic syndrome characterized by a loss of fat mass and muscle mass. Cancer cachexia impairs lifespan and quality of life and can even be a cause of treatment discontinuation (Fearon, Arends, Baracos, Nat Rev Clin Oncol 2013). We showed two years ago that gut microbial dysbiosis occurs in a mouse model of leukemia with cachexia (Bindels et al., Plos ONE 2012) and that administration of short-chain inulin-type fructans (a well-known prebiotic) reduced the accumulation of “leukemic” cells in the liver (Bindels et al, Br J Cancer 2012). Building up on these studies, we tested the hypothesis that two other non-digestible oligosaccharides (pectic oligosaccharides, POS, and inulin, a long-chain inulin-type fructan) modulate gut microbiota and confer benefits on the host in terms of cancer and associated cachexia.

Main challenges and findings

Studying the impact of specific nutrients in cancer cachexia required a multidisciplinary approach. In collaboration with several colleagues, we therefore assessed several morphological, biochemical and molecular host parameters, while gut microbiota was analysed by three complementary molecular approaches (pyrosequencing, PCR-DGGE and qPCR).

We found out that POS and inulin differently impacted the gut microbiome. Inulin reduced cancer cell accumulation in the liver and this could be mediated by the increased levels of propionate and butyrate that were evidenced in the portal blood of the inulin-fed mice. POS blunted fat mass loss, which could be explained by a reduced β-oxydation in the adipose tissue. Complementary analyses were also performed to further investigate the gut-adipose axis.

Towards clinical translation

Our ongoing research in the lab of Prof Delzenne ultimately aims to contribute to the formulation of science-based nutritional advice for cancer patients suffering from cachexia. In a broader context, specific dietary ingredients could constitute novel adjuvant therapies for cachexia and gastrointestinal side-effects of chemotherapy, for instance.

Reading recommendations

  • Fearon K, Arends J, Baracos V (2013) Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 10 (2): 90-99. An extensive and very interesting review on cancer cachexia and current therapeutics, for a broad range of readers.
  • Schwabe RF, Jobin C (2013) The microbiome and cancer. Nat Rev Cancer 13 (11): 800-812. A well-written review on gut microbiota, colorectal cancer and extraintestinal cancers.
  • Bindels LB, Beck R, Schakman O, Martin JC, De Backer FC, Sohet FM, Dewulf EM, Pachikian BD, Neyrinck AM, Thissen JP, Verrax J, Calderon PB, Pot B, Grangette C, Cani PD, Delzenne NM (2012) Restoring Specific Lactobacilli Levels Decreases Inflammation and Muscle Atrophy Markers in an Acute Leukemia Mouse Model. PLoS One 7 (6): e37971. In this study, we brought the first clues that cancer cell inoculation influences the gut microbiota independently of food intake.
  • Lin XB, Dieleman LA, Ketabi A, Bibova I, Sawyer MB, Xue H, Field CJ, Baracos VE, Ganzle MG (2012) Irinotecan (CPT-11) Chemotherapy Alters Intestinal Microbiota in Tumour Bearing Rats. PLoS One 7 (7): e39764. The authors showed that, in a rat model of subcutaneous cancer, tumour bearing state alone induced greater changes than chemotherapy.
  • Sheridan PO, Bindels LB, Saulnier DM, Reid G, Nova E, Holmgren K, O’Toole PW, Bunn J, Delzenne N, Scott KP (2014) Can prebiotics and probiotics improve therapeutic outcomes for undernourished individuals? Gut Microbes 5 (1): 74-82. The proceedings of an ISAPP meeting where we discussed the interest of prebiotics and probiotics in undernutrition.

We thank the people involved in this study: Laure B. Bindels, Audrey M. Neyrinck, Nuria Salazar, Bernard Taminiau, Céline Druart, Giulio G. Muccioli, Emmanuelle François, Christophe Blecker, Aurore Richel, Georges Daube, Jacques Mahillon, Clara G de los Reyes-Gavilán, Patrice D. Cani and Nathalie M. Delzenne.

Laure Bindels
Laure Bindels
I am a PharmD with a PhD in Pharmaceutical Sciences. I did my PhD in nutrition and metabolism in the lab of Prof Delzenne (Université catholique de Louvain), working on the interest of gut microbiota modulation in the control of cancer progression and associated cachexia. I spent a year as a Postdoctoral Research Associate at the University of Nebraska-Lincoln (Prof Ramer-Tait and Prof Jens Walter) working on resistant starches and gut microbiota, where I acquired skills in gnotobiology and bioinformatics analysis. I am now a FNRS Postdoctoral fellow in the lab of Prof Delzenne.