Advertisement

Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 9, pp 2169–2197 | Cite as

Protective effect of the “food-microorganism-SCFAs” axis on colorectal cancer: from basic research to practical application

  • Han Shuwen
  • Da Miao
  • Qi Quan
  • Wu Wei
  • Zhang Zhongshan
  • Zhang Chun
  • Yang XiEmail author
Review – Cancer Research

Abstracts

Background

Recent studies have shown that the short-chain fatty acids (SCFAs) produced by the gut microbiota play a positive role in the development of colorectal cancer (CRC).

Aims

This study aims to elucidate the “food-microorganism-SCFAs” axis and to provide guidance for prevention and intervention in CRC.

Methods

The PubMed, Embase and Cochrane databases were searched from their inceptions to August 2018, and 75 articles and 25 conference abstracts were included and analysed after identification and screening.

Results

The concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. The protective mechanism of SCFAs against CRC has been described in three aspects: epigenetics, immunology and molecular signalling pathways. Many food and plant extracts that were fermented by microorganisms produced SCFAs that play positive roles with preventive and therapeutic effects on CRC. The “food-microorganism-SCFAs” axis was constructed by summarizing the pertinent literature.

Conclusions

This study provides insight into the basic research and practical application of SCFAs by assessing the protective effect of SCFAs on CRC.

Keywords

Diet Microorganism Short-chain fatty acids Butyrate Histone deacetylase Colorectal cancer 

Abbreviations

AC

Aberrant crypt

AhR

Aryl hydrocarbon receptor

Aldh1A2

Aldehyde dehydrogenase 1A2

ANT

Mitochondrial adenine nucleotide translocator

AP-1

Activator protein-1

AWGL

Auto-digested reishi G. lingzhi

AX

Arabinoxylans

BRE

Butyrate-responsive elements

BSG

Brewer’s spent grain

CALB2

Calbindin 2

CRC

Colorectal cancer

DCs

Dendritic cells

DMH

Dimethylhydrazine

ERK

Extracellular signal-regulated kinase

ERK1/2

Extracellular-regulated kinase 1/2

ETBF

Bacteroides fragilis enterotoxin

FFAR2

Free fatty acid receptor 2

FFAR3

Free fatty acid receptor 3

FOS

Fructo-oligosaccharides

HAMS

High-amylose maize starch

HCAR2

Gαi-protein-coupled niacin receptor

HDAC

Histone deacetylase

HFD

High-fat diet

HPD

High-protein diet

IDH1

Isocitrate dehydrogenase 1

IDO1

Indoleamine 2,3-dioxygenase 1

IL

Interleukin

INF

Interferon

LGG

Lactobacillus rhamnosus GG

LGT

Lateral gene transfer

MAPK

Mitogen-Activated Protein Kinase

MLH1

MutL homolog 1

MSH2

MutS protein homolog 2

PDH

Pyruvate dehydrogenase

PKC

Protein Kinase C

SCFAs

Short-chain fatty acids

SLC5A8

Solute Carrier Family 5 Member 8

TET

Ten-eleven translocation

Treg cells

T regulatory cells

α1-AcT

α1-Antichymotrypsin

α-KG

α-Ketoglutarate

Notes

Acknowledgements

This work was supported by the Science Technology Projects of Zhejiang Province (No. 2017C33207), Zhejiang Medical and Health Technology Projects (2019RC283) and Huzhou Public Welfare Technology Application Research Program (2018GY21). The studies that did not involve molecular experiments were analysed to clarify the correlation between SCFAs and CRC and are presented in this table. Most studies showed that the concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. Seven pertinent studies (Panel Nos. 1.3, 1.4, 1.5, 1.8, 1.13, 1.14 and 1.15) that showed a correlation between SCFAs and microorganisms in CRC are also listed in this table. Many studies have been conducted on the molecular mechanisms of SCFA-induced colorectal cancer. A total of 31 articles assessing the molecular mechanisms of SCFA-induced colorectal cancer were included and analysed after identification and screening. As shown in this table, most studies were on butyrate, and the CRC cell model was used as the research subject. The experimental results of SCFAs in different studies are summarized in the results column. Many food and plant extracts fermented by microorganisms can produce SCFAs that play positive roles in the preventive and therapeutic effects on CRC. Pertinent literature assessing the medicines and foods digested by microorganisms to produce SCFAs in CRC have been summarized. Many conference abstracts assessing the SCFAs produced by microorganisms in CRC have been published. A total of 25 abstracts were included in the table after identification and screening according to the inclusion and exclusion criteria.

Author contributions

All authors participated in the conception and design of the study. HS and WW conceived of the study. HS and YX wrote the manuscript. DM and YX designed and drawn the network. HS, QQ, ZZ and ZJ reviewed and sorted out the literature. All authors read and approved the paper.

Funding

This work was supported by the Science Technology Projects of Zhejiang Province (No. 2017C33207), Zhejiang Medical and Health Technology Projects (2019RC283) and Huzhou Public Welfare Technology Application Research Program (2018GY21).

Compliance with ethical standards

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Human and animal rights statement

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

432_2019_2997_MOESM1_ESM.doc (23 kb)
Supplementary material 1 (DOC 23 kb)
432_2019_2997_MOESM2_ESM.doc (24 kb)
Supplementary material 2 (DOC 24 kb)
432_2019_2997_MOESM3_ESM.doc (22 kb)
Supplementary material 3 (DOC 22 kb)
432_2019_2997_MOESM4_ESM.doc (21 kb)
Supplementary material 4 (DOC 21 kb)
432_2019_2997_MOESM5_ESM.doc (33 kb)
Supplementary material 5 (DOC 33 kb)
432_2019_2997_MOESM6_ESM.doc (31 kb)
Supplementary material 6 (DOC 31 kb)

References

  1. Adesida SA et al (2017) Carriage of multidrug resistant Enterococcus faecium and Enterococcus faecalis among apparently healthy humans. Afr J Infect Dis 11(2):83–89Google Scholar
  2. Bishehsari F et al (2018) Dietary fiber treatment corrects the composition of gut microbiota, promotes SCFA production, and suppresses colon carcinogenesis. Genes (Basel) 9(2):102Google Scholar
  3. Cani PD (2018) Human gut microbiome: hopes, threats and promises. GUT 67(9):1716–1725Google Scholar
  4. Chen J, Vitetta L (2018) Inflammation-modulating effect of butyrate in the prevention of colon cancer by dietary fiber. Clin Colorectal Cancer 17(3):e541–e544Google Scholar
  5. Dodoo CC et al (2017) Targeted delivery of probiotics to enhance gastrointestinal stability and intestinal colonisation. Int J Pharm 530(1–2):224–229Google Scholar
  6. Fukugaiti MH et al (2015) High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients. Braz J Microbiol 46(4):1135–1140Google Scholar
  7. Han S et al (2018) Role of intestinal flora in colorectal cancer from the metabolite perspective: a systematic review. Cancer Manag Res 10:199–206Google Scholar
  8. Han S et al (2019) Intestinal microorganisms involved in colorectal cancer complicated with dyslipidosis. Cancer Biol Ther 20(1):81–89Google Scholar
  9. Hester CM et al (2015) Fecal microbes, short chain fatty acids, and colorectal cancer across racial/ethnic groups. World J Gastroenterol 21(9):2759–2769Google Scholar
  10. Hibberd AA et al (2017) Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ Open Gastroenterol 4(1):e000145Google Scholar
  11. Jalaeikhoo H et al (2018) Sixteen years of experience with the treatment of advanced colorectal cancer in Iran; a report from three institutions. Middle East J Dig Dis 10(3):160–168Google Scholar
  12. Kilner J et al (2016) A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids. Mol BioSyst 12(1):93–101Google Scholar
  13. Li Y et al (2017) Human gastrointestinal metabolism of the Cistanches herba water extract in vitro: elucidation of the metabolic profile based on comprehensive metabolite identification in gastric juice, intestinal juice, human intestinal bacteria, and intestinal microsomes. J Agric Food Chem 65(34):7447–7456Google Scholar
  14. Lim SJ et al (2009) Effect of butyrate on the heregulin/ErbB-mediated proliferation of human colorectal cancer cells. Mol Med Rep 2(3):497–502Google Scholar
  15. Meehan CJ, Beiko RG (2014) A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria. Genome Biol Evol 6(3):703–713Google Scholar
  16. Mu C et al (2016) The colonic microbiome and epithelial transcriptome are altered in rats fed a high-protein diet compared with a normal-protein diet. J Nutr 146(3):474–483Google Scholar
  17. Narsing RM, Xiao M, Li WJ (2017) Fungal and bacterial pigments: secondary metabolites with wide applications. Front Microbiol 8:1113Google Scholar
  18. Ni Y et al (2017) A metagenomic study of the preventive effect of Lactobacillus rhamnosus GG on intestinal polyp formation in Apc(Min/+) mice. J Appl Microbiol 122(3):770–784Google Scholar
  19. Nowak A, Slizewska K, Otlewska A (2015) Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens. Regul Toxicol Pharmacol 73(3):938–946Google Scholar
  20. Pan P et al (2018) Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors. Int J Cancer 143(4):886–896Google Scholar
  21. Paritsky M et al (2015) Association of Streptococcus bovis presence in colonic content with advanced colonic lesion. World J Gastroenterol 21(18):5663–5667Google Scholar
  22. Quagliariello A et al (2016) Effect of bifidobacterium breve on the intestinal microbiota of coeliac children on a gluten free diet: a pilot study. Nutrients 8(10):660Google Scholar
  23. Rezasoltani S et al (2017) Gut microbiota, epigenetic modification and colorectal cancer. Iran J Microbiol 9(2):55–63Google Scholar
  24. Saetang J, Sangkhathat S (2017) Diets link metabolic syndrome and colorectal cancer development (review). Oncol Rep 37(3):1312–1320Google Scholar
  25. Sebastian C, Mostoslavsky R (2014) Untangling the fiber yarn: butyrate feeds Warburg to suppress colorectal cancer. Cancer Discov 4(12):1368–1370Google Scholar
  26. Shi Y et al (2017) Synthetic multispecies microbial communities reveals shifts in secondary metabolism and facilitates cryptic natural product discovery. Environ Microbiol 19(9):3606–3618Google Scholar
  27. Shuwen H et al (2018) Competitive endogenous RNA in colorectal cancer: a systematic review. Gene 645:157–162Google Scholar
  28. Singh R et al (2017) Microbial metabolites in nutrition, healthcare and agriculture. 3 Biotech 7(1):15Google Scholar
  29. Sinha R et al (2016) Fecal microbiota, fecal metabolome, and colorectal cancer interrelations. PLoS One 11(3):e0152126Google Scholar
  30. Sun M et al (2017) Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J Gastroenterol 52(1):1–8Google Scholar
  31. Tak KH, Ahn E, Kim E (2017) Increase in dietary protein content exacerbates colonic inflammation and tumorigenesis in azoxymethane-induced mouse colon carcinogenesis. Nutr Res Pract 11(4):281–289Google Scholar
  32. Thirabunyanon M, Hongwittayakorn P (2013) Potential probiotic lactic acid bacteria of human origin induce antiproliferation of colon cancer cells via synergic actions in adhesion to cancer cells and short-chain fatty acid bioproduction. Appl Biochem Biotechnol 169(2):511–525Google Scholar
  33. Vakhitov TY, Chalisova N, Sitkin SI (2016) Effect of carboxylic acids of gut microbial origin on host cell proliferation in organotypic tissue cultures. Eksp Klin Gastroenterol 12(12):73–82Google Scholar
  34. Wang X, Yang Y, Huycke MM (2017a) Microbiome-driven carcinogenesis in colorectal cancer: models and mechanisms. Free Radic Biol Med 105:3–15Google Scholar
  35. Wang X et al (2017b) Gut flora profiling and fecal metabolite composition of colorectal cancer patients and healthy individuals. Exp Ther Med 13(6):2848–2854Google Scholar
  36. Wang Z et al (2018) Comparison of fecal collection methods for microbiome and metabolomics studies. Front Cell Infect Microbiol 8:301Google Scholar
  37. Wu JC et al (2018) Polymethoxyflavones prevent benzo[a]pyrene/dextran sodium sulfate-induced colorectal carcinogenesis through modulating xenobiotic metabolism and ameliorate autophagic defect in ICR mice. Int J Cancer 142(8):1689–1701Google Scholar
  38. Yoon JS et al (2014) Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol 29(1):52–59Google Scholar
  39. Yu Z et al (2018) Beneficial effects of extracellular polysaccharide from Rhizopus nigricans on the intestinal immunity of colorectal cancer mice. Int J Biol Macromol 115:718–726Google Scholar
  40. Zeng H et al (2018) Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet. J Nutr Biochem 54:18–27Google Scholar
  41. Zhang M et al (2016) Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats. BMC Gastroenterol 16(1):84Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medical OncologyHuzhou Central Hospital, Affiliated Central Hospital HuZhou UniversityHuzhouChina
  2. 2.Medical College of NursingHuzhou UniversityHuzhouChina
  3. 3.Department of Digestive SystemHuzhou Central Hospital, Affiliated Central Hospital HuZhou UniversityHuzhouChina
  4. 4.Department of MedicineHuzhou UniversityHuzhouChina
  5. 5.Department of Infectious DiseaseHuzhou Central Hospital, Affiliated Central Hospital HuZhou UniversityHuzhouChina
  6. 6.Department of Intervention and RadiotherapyHuzhou Central Hospital, Affiliated Central Hospital HuZhou UniversityHuzhouChina

Personalised recommendations