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Diet, Metabolites, and “Western-Lifestyle” Inflammatory Diseases
Open accessAbstract
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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“Accumulating experimental animal data indicate that gut microbial production of these short-chain fatty acids from dietary fiber can suppress the development of several inflammatory, autoimmune, and allergic disease (92).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [92]
In the citing paper
“Some of the beneficial effects of these microbiome-derived metabolites are thought to be mediated by the binding to specific G-protein–coupled receptors expressed on enteroendocrine and immune cells (92).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [92]
In the citing paper
“In contrast, multigenerational exposure to a Western diet poor in “microbiota-accessible carbohydrates” result in the extinction of specific bacterial lineages, which might negatively influence the maturation and function of the immune system, and increase the risk of developing a range of metabolic, inflammatory, allergic, and autoimmune diseases (92,94,98).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [92]
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“Acetylation can also promote the activation, nuclear translocation and DNA binding of transcription factors (such as STAT3, NF-kB, FoxP3, N-FAT and RUNX1).(118,218,219) In addition, sodium propionate (SP) affects the expression of survivin and p21, inducing cell cycle arrest especially in the G2/M phase, and then lead…”
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“Strong epidemiological evidences support the concept that diet underpins the rise in chronic inflammatory diseases such as IBD, diabetes, or asthma [3, 5, 6].”
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Inhibition of inflammation by berberine: Molecular mechanism and network pharmacology analysis
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Food, immunity, and the microbiome
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“[77] [78] [79] Other studies show that the elderly living in the community with healthy diets 78 have higher gut microbiota diversity than those in longstay residential care who have a less diverse diet.”
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“Diet-related, either or not microbiota-derived, metabolites engage the upregulation of metabolite-sensing G-protein-coupled and other receptors on intestinal epithelial cells, as shown in laboratory animals [29].”
BackgroundThe nutrition‐gut microbiome‐physiology axis and allergic diseases
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Metabolic and Vascular Effect of the Mediterranean Diet
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“Bacteroidetes (in particular, Bacteroides acidifaciens) have an important role in gut microbiota through the production of high levels of short-chain fatty acids, including acetate, propionate, or butyrate, in fact many experimental animal data suggest that their high levels can discontinue the progress of several inf…”
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“This variety of local metabolites affect on mucosal and systemic immune maturation and are involved in multiple immune signaling pathways with the participation of macrophages, dendritic cells (DCs), T cells, and innate lymphoid cells (ILCs) (110, 111).”
BackgroundEvolution, human-microbe interactions, and life history plasticity
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“Some microbiota-derived signals (Figure 3), notably those that signal via ‘‘metabolite-sensing’’ G-protein-coupled receptors (GPCR) or by inhibiting histone deacetylase (HDAC) and so driving epigenetic changes, are equally relevant to metabolism and to immunoregulation.((20)) This close link might be due to the large…”
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“Two of the most well-studied mechanisms through which butyrate has been shown to modulate immune cell function are inhibition of HDAC activity and signaling through GPRs (4, 5, 9, 10, 18).”
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Prebiotics, Probiotics, Synbiotics, Paraprobiotics and Postbiotic Compounds in IBD
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Piazzon, M. C., Calduch-Giner, J. À., Fouz, B., Estensoro, I., Simó‐Mirabet, P., Puyalto, M., Karalazos, V., Palenzuela, O. R., Sitjà‐Bobadilla, A., & Pérez‐Sánchez, J. (2017) · Microbiome · doi:10.1186/s40168-017-0390-3 · Cited by 245
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“Inoculation of SCFAs producing bacteria can increase Bacteroidetes abundances while reducing Firmicutes, and improve balance in the gut bacterial structure.(34) Overall, these data have led to emerging interests in the regulatory function of SCFAs in a wide range of immune cells, including both innate and adaptive cel…”
BackgroundZhang, W., Zou, G.-L., Li, B., Du, X., Sun, Z., Sun, Y., & Jiang, X. (2020) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2002.02044 · Cited by 238
“8 Effects of FMT on SCFA Production SCFAs act as key bacterial metabolites, mainly composed of acetate, propionate and butyrate in the intestine, which are beneficial for human health [58, 59].”
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An exposome perspective: Early-life events and immune development in a changing world
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“Interestingly, 19 of 90 subjects had discordant OTU type and metabotype, suggesting that other factors besides the microbiome such as diet also could influence the metabolome.(49) A strength of this study was that its central finding (a disease-related microbial community type detectable in healthy subjects) also was…”
BackgroundGut Microbiota Metabolism and Interaction with Food Components
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“Hence, the principal activities of SCFAs are the following [51]: (1) triggering of Foxp3+ T regulatory (Treg) cells and tolerance; (2) induction of IgA secretion from B cells; (3) “competitive exclusion”, due to high-fiber diet that spreads commensal bacteria and limits the access of pathogenic bacteria to the gut epi…”
BackgroundInfluentialLeveraging diet to engineer the gut microbiome
Wolter, M., Grant, E. T., Boudaud, M., Steimle, A., Pereira, G. V., Martens, E. C., & Desai, M. S. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00512-7 · Cited by 211
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Role of Short Chain Fatty Acid Receptors in Intestinal Physiology and Pathophysiology
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“Gut microbial structural components and other metabolites also affect host physiology with potential bearings on SCFA levels and these receptors [reviewed in (169, 199)].”
Metadata
- Authors
- Thorburn, A. N., Macia, L., & Mackay, C. R.
- Affiliations
- Monash University (AU)
- Corresponding author
- Mackay, Charles R.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 40
- Issue
- 6
- Pages
- 833-842
- ISSN
- 1074-7613 (ISSN-L)
- 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
- 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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