Review article: short chain fatty acids as potential therapeutic
agents in human gastrointestinal and inflammatory disorders
P. A. Gill
M. C. van Zelm
J. G. Muir
P. R. Gibson
Department of Gastroenterology, Central
Clinical School, Monash University and
Alfred Hospital, Melbourne, Vic., Australia
Department of Immunology and Pathology,
Central Clinical School, Monash University
and Alfred Hospital, Melbourne, Vic,
Prof. PR Gibson, Department of
Gastroenterology, Central Clinical School,
Monash University and Alfred Hospital,
Melbourne, Vic., Australia.
PAG is supported by a scholarship from the
Central Clinical School, Monash University.
MCvZ is supported by NHMRC Senior
Research Fellowship GNT1117687. JGM is
supported by NHMRC Senior Research
Background: Butyrate, propionate and acetate are short chain fatty acids (SCFA),
important for maintaining a healthy colon and are considered as protective in col-
orectal carcinogenesis. However, they may also regulate immune responses and the
composition of the intestinal microbiota. Consequently, their importance in a variety
of chronic inflammatory diseases is emerging.
Aims: To review the physiology and metabolism of SCFA in humans, cellular and
molecular mechanisms by which SCFA may act in health and disease, and
approaches for therapeutic delivery of SCFA.
Methods: A PubMed literature search was conducted for clinical and pre-clinical
studies using search terms: ‘dietary fibre’, short-chain fatty acids’, ‘acetate’, ‘propi-
onate’, ‘butyrate’, ‘inflammation’, ‘immune’, ‘gastrointestinal’, ‘metabolism’.
Results: A wide range of pre-clinical evidence supports roles for SCFA as modula-
tors of not only colonic function, but also multiple inflammatory and metabolic pro-
cesses. SCFA are implicated in many autoimmune, allergic and metabolic diseases.
However, translating effects of SCFA from animal studies to human disease is lim-
ited by physiological and dietary differences and by the challenge of delivering suffi-
cient amounts of SCFA to the target sites that include the colon and the systemic
circulation. Development of novel targeted approaches for colonic delivery, com-
bined with postbiotic supplementation, may represent desirable strategies to achieve
adequate targeted SCFA delivery.
Conclusions: There is a large array of potential disease-modulating effects of SCFA.
Adequate targeted delivery to the sites of action is the main limitation of such appli-
cation. The ongoing development and evaluation of novel delivery techniques offer
potential for translating promise to therapeutic benefit.
The Handling Editor for this article was Professor Jonathan Rhodes, and this uncommis-
sioned review was accepted for publication after full peer-review.
Received: 20 December 2017
First decision: 9 February 2018
Accepted: 6 April 2018
Aliment Pharmacol Ther. 2018;48:15–34. wileyonlinelibrary.com/journal/apt © 2018 John Wiley & Sons Ltd