Cargando…

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

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 import...

Descripción completa

Detalles Bibliográficos
Autores principales: Ubachs, Jorne, Ziemons, Janine, Soons, Zita, Aarnoutse, Romy, van Dijk, David P.J., Penders, John, van Helvoort, Ardy, Smidt, Marjolein L., Kruitwagen, Roy F.P.M., Baade‐Corpelijn, Lieke, Olde Damink, Steven W.M., Rensen, Sander S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718054/
https://www.ncbi.nlm.nih.gov/pubmed/34609073
http://dx.doi.org/10.1002/jcsm.12804
_version_ 1784624640459538432
author Ubachs, Jorne
Ziemons, Janine
Soons, Zita
Aarnoutse, Romy
van Dijk, David P.J.
Penders, John
van Helvoort, Ardy
Smidt, Marjolein L.
Kruitwagen, Roy F.P.M.
Baade‐Corpelijn, Lieke
Olde Damink, Steven W.M.
Rensen, Sander S.
author_facet Ubachs, Jorne
Ziemons, Janine
Soons, Zita
Aarnoutse, Romy
van Dijk, David P.J.
Penders, John
van Helvoort, Ardy
Smidt, Marjolein L.
Kruitwagen, Roy F.P.M.
Baade‐Corpelijn, Lieke
Olde Damink, Steven W.M.
Rensen, Sander S.
author_sort Ubachs, Jorne
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8718054
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-87180542022-01-06 Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients Ubachs, Jorne Ziemons, Janine Soons, Zita Aarnoutse, Romy van Dijk, David P.J. Penders, John van Helvoort, Ardy Smidt, Marjolein L. Kruitwagen, Roy F.P.M. Baade‐Corpelijn, Lieke Olde Damink, Steven W.M. Rensen, Sander S. J Cachexia Sarcopenia Muscle Original Articles 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. John Wiley and Sons Inc. 2021-10-05 2021-12 /pmc/articles/PMC8718054/ /pubmed/34609073 http://dx.doi.org/10.1002/jcsm.12804 Text en © 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Ubachs, Jorne
Ziemons, Janine
Soons, Zita
Aarnoutse, Romy
van Dijk, David P.J.
Penders, John
van Helvoort, Ardy
Smidt, Marjolein L.
Kruitwagen, Roy F.P.M.
Baade‐Corpelijn, Lieke
Olde Damink, Steven W.M.
Rensen, Sander S.
Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients
title Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients
title_full Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients
title_fullStr Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients
title_full_unstemmed Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients
title_short Gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients
title_sort gut microbiota and short‐chain fatty acid alterations in cachectic cancer patients
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718054/
https://www.ncbi.nlm.nih.gov/pubmed/34609073
http://dx.doi.org/10.1002/jcsm.12804
work_keys_str_mv AT ubachsjorne gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT ziemonsjanine gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT soonszita gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT aarnoutseromy gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT vandijkdavidpj gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT pendersjohn gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT vanhelvoortardy gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT smidtmarjoleinl gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT kruitwagenroyfpm gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT baadecorpelijnlieke gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT oldedaminkstevenwm gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients
AT rensensanders gutmicrobiotaandshortchainfattyacidalterationsincachecticcancerpatients