Gastrointestinal cancers: Influence of gut microbiota, probiotics and prebiotics

doi:10.1016/j.canlet.2013.08.013

Cancer Letters

Volume 345, Issue 2, 10 April 2014, Pages 258-270

https://doi.org/10.1016/j.canlet.2013.08.013 Get rights and content

Highlights

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Gut microbiota is a key element for gastrointestinal cancers (especially of the colon and stomach)
•
Carcinogenesis may be induced by gut microbiota through complex and various mechanisms
•
Probiotics and prebiotics have anticarcinogenic effects, mainly in vitro and in animal studies
•
In human GI cancers, probiotics and prebiotics are promising tools in prevention and/or therapy.

Abstract

Cancers of the gastrointestinal (GI) tract continue to represent a major health problem, despite progress in therapy. Gut microbiota is a key element related to the genesis of GI cancers, countless papers addressing this burning issue across the world. We provide an updated knowledge of the involvement of gut microbiota in GI tumorigenesis, including its underlying mechanisms. We present also a comprehensive review of the evidence from animal and clinical studies using probiotics and/or prebiotics in the prevention and/or therapy of GI tumours, of GI cancer therapy-related toxicity and of post-operative complications. We summarize the anticarcinogenic mechanisms of these biotherapeutics from in vitro, animal and clinical interventions. More research is required to reveal the interactions of microflora with genetic, epigenetic and immunologic factors, diet and age, before any firm conclusion be drawn. Well-designed, randomized, double blind, placebo-controlled human studies using probiotics and/or prebiotics, with adequate follow-up are necessary in order to formulate directions for prevention and therapy.

Introduction

Cancers of the gastrointestinal (GI) tract continue to represent a major health problem, despite progress in therapy, accounting for 25% of all cancers and 9% of all causes of cancer death in the world [1]. In 2005, the worldwide burden of oesophageal cancer was estimated to be 500,000 new cases. Gastric cancer (GC) is the fourth most common cancer and the second cause of cancer-related death worldwide, accounting for nearly 1,000,000 new cases annually and over 850,000 deaths at the same time [2], [3], [4]. Overall GC incidence is constantly decreasing, possibly due to the fall in the H. pylori (HP) prevalence [5]. Neoplasms of the small intestine are rare throughout the world, global incidence ranging from 0.3 to 2.0 per 100,000 [6]. Colorectal cancer (CRC) is the third most frequent cancer worldwide (more than 1 million new cases/year) and the fourth most common cause of cancer death, with about 500,000 deaths annually [4].

The multi-steps mechanisms associated with GI cancer prevention and development are largely unknown, being the subject of much research. GI cancers are considered to be multifactorial diseases, the end result of complicated relationships between genetics, epigenetics, immunity, environment (including geographical area and socio-economic status), diet and lifestyle, all of which could interact with the GI microflora, altering its profiles and functions during the tumour genesis and growth [5], [7].

Section snippets

Composition and beneficial activities

The normal intestinal microbiota represents a complex, dynamic, and diverse collection of microorganisms, which usually inhabit the GI tract [8], [9]. Normally, between this flora and the human host a mutually beneficial long-term symbiotic relationship is established, where the host contributes essential nutrients necessary for the survival of the microbiota and the latter fulfils multiple roles for the host [9]. The development of sophisticated culture independent methods allowed the

Probiotics, prebiotics and synbiotics in GI cancers

Since microbiota is involved in the genesis of GI cancers, its beneficial manipulation may have cancer-preventive/therapeutic effects [5]. Most studies have been performed in CRC, but other cancer locations (like stomach and oesophagus) have begun to be explored as well. Classically, probiotics (PRO) are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host [97]. Most strains belong to L and BF, but Streptococcus thermophilus, Enterococcus,

Conclusions and future directions

There is an ample body of evidence that gut microbiota contributes to GI tumorigenesis. Numerous in vitro studies and animal models show remarkable evidence that PRO (especially from the genera L and BF), PRE (especially inulin ± oligofructose) and SYN (combination of PRO and PRE) exert important anticarcinogenic effects. However, there is not enough evidence from human studies to strongly support the use of these biotherapeutics in prevention/therapy of GI cancers. Studies are very heterogenic

Conflict of Interest

None.

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Mini-reviewGastrointestinal cancers: Influence of gut microbiota, probiotics and prebiotics

Highlights

Abstract

Introduction

Section snippets

Composition and beneficial activities

Probiotics, prebiotics and synbiotics in GI cancers

Conclusions and future directions

Conflict of Interest

Ann. Epidemiol.

Med. Hypotheses.

Cell. Host. Microbe.

Int. J. Pharm.

Mutat. Res.

J. Nutr.

Am. J. Clin. Nutr.

Best. Pract. Res. Clin. Gastroenterol.

J. Vasc. Surg.

FEMS Microbiol. Lett.

J. Lipid. Res.

Am. J. Clin. Nutr.

J. Nutr. Biochem.

Chemoprevention in gastrointestinal adenocarcinoma: for few but not for all?

Minerva. Gastroenterol. Dietol.

Gastric cancer: basic aspects

Helicobacter

Evolutionary history of the Helicobacter pylori genome: implications for gastric carcinogenesis

Gut. Liver.

Intestinal microbiota, probiotics and human gastrointestinal cancers

J. Gastrointest. Cancer.

Intestinal microbiota: does it play a role in diseases of the neonate?

Neoreviews

The gut microbiota in the metagenomics era: sometimes a friend, sometimes a foe

Roum. Arch. Microbiol. Immunol.

A human gut microbial gene catalogue established by metagenomic sequencing

Nature

Towards the human intestinal microbiota phylogenetic core

Environ. Microbiol.

Gut microbiota, obesity and diabetes

Ann. Nestlé. (Engl.)

The gut flora as a forgotten organ

EMBO. Rep.

Butyrate and Wnt signaling: a possible solution to the puzzle of dietary fiber and colon cancer risk?

Cell. Cycle.

Differential antineoplastic effects of butyrate in cells with and without a functioning DNA mismatch repair

Nutr. Cancer

Butyrate-induced cell death and differentiation are associated with distinct patterns of ROS in HT29-derived human colon cancer cells

Dig. Dis. Sci.

Disappearing microbiota: Helicobacter pylori protection against esophageal adenocarcinoma

Cancer Prev. Res. (Phila)

Helicobacter pylori and esophageal cancer risk: a meta-analysis

Cancer Prev. Res.

Childhood and Correa model of carcinogenesis

Med. Arh.

Epidemiology of cancer of the small intestine

World J. Gastrointest. Oncol.

New insights into the impact of the intestinal microbiota on health and disease: a symposium report

Br. J. Nutr.

The role of the gastrointestinal microflora in colorectal cancer

Curr. Pharm. Des.

Bile acid concentrations, cytotoxicity, and pH of fecal water from patients with colorectal adenomas

Dig. Dis. Sci.

Genotoxic activity in human faecal water and the role of bile acids: A study using the Comet assay

Carcinogenesis

Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity

Int. J. Oncol.

Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor chain and p53 double-knockout mice

Cancer Res.

Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility

PLoS One

Towards the human colorectal cancer microbiome

PLoS One

Gut microbiota: next frontier in understanding human health and development of biotherapeutics

Biologics

The causes of intestinal dysbiosis: a review

Altern. Med. Rev.

Upper gastrointestinal microbiota and digestive diseases

World J. Gastroenterol.

Oesophageal bacterial biofilm changes in gastro-oesophageal reflux disease, Barrett’s and oesophageal carcinoma: association or causality?

Aliment. Pharmacol. Ther.

Mini-review
Gastrointestinal cancers: Influence of gut microbiota, probiotics and prebiotics