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      Colorectal cancer and inulin supplementation: the good, the bad, and the unhelpful

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          Abstract

          The prebiotic inulin has been vaunted for its potential to reduce the risk of colorectal cancer. Inulin fermentation resulting in the production of short-chain fatty acids, primarily butyrate, has been reported to be associated with properties that are beneficial for gut health and has led to an increased consumption of inulin in the Western population through processed food and over-the-counter dietary supplements. However, in clinical trials, there is limited evidence of the efficacy of inulin in preventing colorectal cancer. Moreover, recent data suggest that improper inulin consumption may even be harmful for gastro-intestinal health under certain circumstances. The main objective of this review is to provide insight into the beneficial and potentially detrimental effects of inulin supplementation in the context of colorectal cancer prevention and enhancement of treatment efficacy.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases

            Daniela Parada Venegas, Marjorie K. De la Fuente, Glauben Landskron … (2019)
            Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.
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              Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies

              NaNa Keum, Edward Luciano Giovannucci (2019)
              Globally, colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death. Arising through three major pathways, including adenoma-carcinoma sequence, serrated pathway and inflammatory pathway, CRC represents an aetiologically heterogeneous disease according to subtyping by tumour anatomical location or global molecular alterations. Genetic factors such as germline MLH1 and APC mutations have an aetiologic role, predisposing individuals to CRC. Yet, the majority of CRC is sporadic and largely attributable to the constellation of modifiable environmental risk factors characterizing westernization (for example, obesity, physical inactivity, poor diets, alcohol drinking and smoking). As such, the burden of CRC is shifting towards low-income and middle-income countries as they become westernized. Furthermore, the rising incidence of CRC at younger ages (before age 50 years) is an emerging trend. This Review provides a comprehensive summary of CRC epidemiology, with emphasis on modifiable lifestyle and nutritional factors, chemoprevention and screening. Overall, the optimal reduction of CRC incidence and mortality will require concerted efforts to reduce modifiable risk factors, to leverage chemoprevention research and to promote population-wide and targeted screening.
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                Author and article information

                Contributors
                Manon Oliero
                Ahmed Amine Alaoui
                Claire McCartney
                Manuela M Santos:
                ORCID: https://orcid.org/0000-0003-3497-0585
                Journal
                Journal ID (nlm-ta): Gastroenterol Rep (Oxf)
                Journal ID (iso-abbrev): Gastroenterol Rep (Oxf)
                Journal ID (publisher-id): gastro
                Title: Gastroenterology Report
                Publisher: Oxford University Press
                ISSN (Electronic): 2052-0034
                Publication date Collection: 2024
                Publication date (Electronic): 09 July 2024
                Publication date PMC-release: 09 July 2024
                Volume: 12
                Electronic Location Identifier: goae058
                Affiliations
                Nutrition and Microbiome Laboratory, Institut du cancer de Montréal, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM) , Montréal, QC, Canada
                Nutrition and Microbiome Laboratory, Institut du cancer de Montréal, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM) , Montréal, QC, Canada
                Department of Medicine, Faculty of Medicine, Université de Montréal , Montréal, QC, Canada
                Nutrition and Microbiome Laboratory, Institut du cancer de Montréal, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM) , Montréal, QC, Canada
                Nutrition and Microbiome Laboratory, Institut du cancer de Montréal, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM) , Montréal, QC, Canada
                Department of Medicine, Faculty of Medicine, Université de Montréal , Montréal, QC, Canada
                Author notes
                Corresponding author. Nutrition and Microbiome Laboratory, Institut du cancer de Montreal, Centre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), 900 rue Saint-Denis, Montréal, Québec H2X 0A9, Canada. Tel: +1-514-890-8000 ext. 28928; Email: manuela.santos@ 123456umontreal.ca
                Author information
                https://orcid.org/0000-0003-3497-0585
                Article
                Publisher ID: goae058
                DOI: 10.1093/gastro/goae058
                PMC ID: 11231048
                PubMed ID: 38984069
                SO-VID: a4d54a43-28e8-4feb-a575-841e6bb3f7cc
                Copyright © © The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 2 January 2024
                Date revision received : 15 March 2024
                Date accepted : 20 May 2024
                Page count
                Pages: 11
                Funding
                Funded by: Canadian Institutes of Health Research, DOI 10.13039/501100000024;
                Award ID: PJT-159775
                Funded by: Natural Sciences and Engineering Research Council of Canada, DOI 10.13039/501100000038;
                Categories
                Subject: Review Article
                Subject: AcademicSubjects/MED00260

                Keywords: colorectal cancer,inulin,prebiotic,gut microbiota,short-chain fatty acids
                Data availability:
                Keywords: colorectal cancer, inulin, prebiotic, gut microbiota, short-chain fatty acids

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