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



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).


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


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.


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.


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


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



Aberrant crypt


Aryl hydrocarbon receptor


Aldehyde dehydrogenase 1A2


Mitochondrial adenine nucleotide translocator


Activator protein-1


Auto-digested reishi G. lingzhi




Butyrate-responsive elements


Brewer’s spent grain


Calbindin 2


Colorectal cancer


Dendritic cells




Extracellular signal-regulated kinase


Extracellular-regulated kinase 1/2


Bacteroides fragilis enterotoxin


Free fatty acid receptor 2


Free fatty acid receptor 3




High-amylose maize starch


Gαi-protein-coupled niacin receptor


Histone deacetylase


High-fat diet


High-protein diet


Isocitrate dehydrogenase 1


Indoleamine 2,3-dioxygenase 1






Lactobacillus rhamnosus GG


Lateral gene transfer


Mitogen-Activated Protein Kinase


MutL homolog 1


MutS protein homolog 2


Pyruvate dehydrogenase


Protein Kinase C


Short-chain fatty acids


Solute Carrier Family 5 Member 8


Ten-eleven translocation

Treg cells

T regulatory cells







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.


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

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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

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