Cited by 879Gut microbiota and healthAdipokines, Inflammation, and Metabolic DiseasesGastrointestinal motility and disorders

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Diet, Metabolites, and “Western-Lifestyle” Inflammatory Diseases

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Thorburn, Alison N., Macia, Laurence, Mackay, Charles R.·2014·Immunity

DOI 10.1016/j.immuni.2014.05.014

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Abstract

One explanation for the increased incidence of allergies, asthma, and even some autoimmune diseases has been the hygiene hypothesis. However, recent studies also highlight an important role for diet and bacterial metabolites in controlling various immune pathways, including gut and immune homeostasis, regulatory T cell biology, and inflammation. Dietary-related metabolites engage "metabolite-sensing" G-protein-coupled receptors, such as GPR43, GPR41, GPR109A, GPR120, and GPR35. These receptors are expressed on immune cells and some gut epithelial cells and generally mediate a direct anti-inflammatory effect. Insufficient intake of "healthy foodstuffs" adversely affects the production of bacterial metabolites. These metabolites and those derived directly from food drive beneficial downstream effects on immune pathways. We propose that insufficient exposure to dietary and bacterial metabolites might underlie the development of inflammatory disorders in Western countries. This review highlights what is currently known about diet, metabolites, and their associated immune pathways in relation to the development of inflammatory disease.

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Background
Short-chain fatty acid levels in stools of patients with inflammatory bowel disease are lower than those in healthy subjects
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The linkage of gut microbiota and the property theory of traditional Chinese medicine (TCM): Cold-natured and sweet-flavored TCMs as an example
Yang, Y., & Wu, C. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116167 · Cited by 24
Human Milk Lipids and Small Metabolites: Maternal and Microbial Origins
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Enzymatic Modification of Corn Starch Influences Human Fecal Fermentation Profiles
Durá, Á., Rose, D. J., & Rosell, C. M. (2017) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.7b01634 · Cited by 24
A Potential Benefit of “Balanced Diet” for Rheumatoid Arthritis
Masuko, K. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00141 · Cited by 24
“Nutrients, in particular dietary fiber, is an important regulator of the gut microbiome (18, 21, 22).”
Background
Zinc Deficiency and Zinc Supplementation in Allergic Diseases
Maywald, M., & Rink, L. (2024) · Biomolecules · doi:10.3390/biom14070863 · Cited by 23
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Harnessing Lactobacillus-derived SCFAs for food and health: Pathways, genes, and functional implications
Nami, Y., Ranjbar, M. S., Aval, M. M., & Haghshenas, B. (2025) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2025.100496 · Cited by 25
On the Verge of a Catastrophic Collapse? The Need for a Multi-Ecosystem Approach to Microbiome Studies
Larsen, O. F. A., & van de Burgwal, L. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.784797 · Cited by 22
Alterations of the gut microbial community structure and function with aging in the spontaneously hypertensive stroke prone rat
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“(2) Given the number of genera that were different between WKY and SHRSP at ages when HT was developing, it is possible that an overall change in the microbial community structure, as opposed to a change in a single or a few bacteria, was responsible the development of HT (Fig.”
Background
A high-calorie diet aggravates LPS-induced pneumonia by disturbing the gut microbiota and Th17/Treg balance
Liu, H., Bai, C., Xian, F., Liu, S., Long, C., Hu, L., Liu, T., & Gu, X. (2022) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ma0322-458rr · Cited by 25
Inulin prebiotic ameliorates type 1 diabetes dictating regulatory T cell homing via CCR4 to pancreatic islets and butyrogenic gut microbiota in murine model
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Meat Intake and the Dose of Vitamin B 3 – Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?
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Dietary patterns and risk of systemic lupus erythematosus in women
Tedeschi, S. K., Barbhaiya, M., Sparks, J. A., Karlson, E. W., Kubzansky, L. D., Roberts, A. L., Willett, W. C., Lü, B., & Costenbader, K. H. (2019) · Lupus · doi:10.1177/0961203319888791 · Cited by 23
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Rueter, K., Prescott, S. L., & Palmer, D. J. (2015) · Journal of Paediatrics and Child Health · doi:10.1111/jpc.12951 · Cited by 23
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Background
Dietary therapies for adult and pediatric inflammatory bowel disease
Deas, J., Shah, N. D., Konijeti, G. G., Lundin, A., Lanser, O., Magavi, P. R., & Ali, S. A. (2024) · Nutrition in Clinical Practice · doi:10.1002/ncp.11146 · Cited by 22
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Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome & Microbiome-Derived Metabolites
Malczewski, A. B., Ketheesan, N., Coward, J. I. G., & Navarro, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.624434 · Cited by 22
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Gong, H., Zeng, R., Li, Q., Liu, Y., Zuo, C., Ren, J., Zhao, L., & Lin, M. (2022) · International Ophthalmology · doi:10.1007/s10792-021-02190-5 · Cited by 22
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The effects of dietary patterns and food groups on symptomatic osteoarthritis: A systematic review
Zeng, J., Franklin, D. K., Das, A., & Hirani, V. (2022) · Nutrition & Dietetics · doi:10.1111/1747-0080.12781 · Cited by 22
“57,59 One study discovered that fruit and vegetable fibre were inversely associated with moderate knee pain and cereal fibre and fruit and vegetable fibre were inversely associated with severe knee pain, 37 whereas the other failed to demonstrate significant effects of fibre from each food group.”
Harnessing AI and Gut Microbiome Research for Precision Health
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“gut-microbiome-derived metabolites have also been implicated in human chronic inflammatory diseases.(53) These”
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Mediterranean diet and osteoarthritis: an update
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Gut Microbiota-Modulated Metabolomic Profiling Shapes the Etiology and Pathogenesis of Autoimmune Diseases
Tsai, Y.-W., Dong, J.-L., Jian, Y.-J., Fu, S., Chien, M., Liu, Y., Hsu, C.-Y., & Sytwu, H. (2021) · Microorganisms · doi:10.3390/microorganisms9091930 · Cited by 21
Understanding the Effects of Metabolites on the Gut Microbiome and Severe Acute Pancreatitis
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Pu, K., Yang, F., Tang, Q., Yang, G., & Xu, C. S. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1333623 · Cited by 24
“It can also increase gut short-chain fatty acid (SCFA) level, which have shown to suppress the development of several in ﬂ ammatory, autoimmune, and allergic disease (76).”
Background
The impact of long-term dietary pattern of fecal donor on in vitro fecal fermentation properties of inulin
Yang, J., & Rose, D. J. (2015) · Food & Function · doi:10.1039/c5fo00987a · Cited by 21
Fatty Acids, Gut Bacteria, and Immune Cell Function
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Self-citation
The impact of high‐salt diet on asthma in humans and mice: Effect on specific T‐cell signatures and microbiome
Musiol, S., Harris, C. P., Gschwendtner, S., Burrell, A., Amar, Y., Schnautz, B., Renisch, D., Braun, S. C., Haak, S., Schloter, M., et al. (2024) · Allergy · doi:10.1111/all.16148 · Cited by 22
Fructooligosaccharides benefits on glucose homeostasis upon high-fat diet feeding require type 2 conventional dendritic cells
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Effects of micronutrients and macronutrients on risk of allergic disease in the European population: a Mendelian randomization study
Zeng, X., Wu, Z., Pan, Y., Ma, Y., Chen, Y., & Zhao, Z. (2024) · Food and Agricultural Immunology · doi:10.1080/09540105.2024.2442369 · Cited by 20
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Mukherjee, A., Farsi, D. N., García-Gutiérrez, E., Akan, E., Salas-Millán, J. Á., Angelovski, L., Bintsis, Τ., Gérard, A., Güley, Z., Kabakcı, S. A., et al. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1668889 · Cited by 26
“Indeed, recent research suggests that the industrialised, Western diet has contributed to the rise of several contemporary chronic metabolic, immune and “lifestyle” diseases (2, 3).”
Role of Short Chain Fatty Acids and Apolipoproteins in the Regulation of Eosinophilia-Associated Diseases
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Commensal Bifidobacterium Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
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“A rapid increase in the incidence of IBD, which is broadly divided into Crohn’s disease (CD) and ulcerative colitis (UC), has been observed in Asia owing to the westernization of diet and lifestyle (14).”
Background

Authors: Thorburn, A. N., Macia, L., & Mackay, C. R.
Affiliations: Monash University (AU)
Corresponding author: Mackay, Charles R.
ORCID: Macia, Laurence
Mackay, Charles R.
Venue: Immunity
Publisher: Elsevier BV
Published: 2014-06
Volume: 40
Issue: 6
Pages: 833-842
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2014.05.014
OpenAlex: W2008993230
Cited by: 879
References: 103
Citations by year: 2026: 27 · 2025: 32 · 2024: 80 · 2023: 77 · 2022: 83 · 2021: 114 · 2020: 82 · 2019: 88 · 2018: 71 · 2017: 67 · 2016: 77 · 2015: 68 · 2014: 11
FWCI: 7.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 383 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: Australian Research Council
National Health and Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: diet, bacterial metabolites, Western lifestyle, inflammatory diseases, hygiene hypothesis, G protein-coupled receptors, GPR43, GPR41, GPR109A, GPR120, GPR35, gut immune homeostasis, regulatory T cells, anti-inflammatory signaling, dietary metabolites, allergy, asthma, autoimmune disease
MeSH terms: Autoimmune Diseases, Bacterial Proteins, Diet, Humans, Hypersensitivity, Inflammation, Life Style, Gastrointestinal Tract, Receptors, G-Protein-Coupled, Metabolome, Microbiota

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Diet, Metabolites, and “Western-Lifestyle” Inflammatory Diseases

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