Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms

Al-Lahham, Sa'ad H.; Peppelenbosch, Maikel P.; Roelofsen, Han; Vonk, Roel J.; Venema, Koen

doi:10.1016/j.bbalip.2010.07.007

Cited by 614Gut microbiota and healthAdipokines, Inflammation, and Metabolic DiseasesPeroxisome Proliferator-Activated Receptors

Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms

Al-Lahham, Sa'ad H., Peppelenbosch, Maikel P., Roelofsen, Han, Vonk, Roel J., Venema, Koen·2010·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

DOI 10.1016/j.bbalip.2010.07.007

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Abstract

Undigested food is fermented in the colon by the microbiota and gives rise to various microbial metabolites. Short-chain fatty acids (SCFA), including acetic, propionic and butyric acid, are the principal metabolites produced. However, most of the literature focuses on butyrate and to a lesser extent on acetate; consequently, potential effects of propionic acid (PA) on physiology and pathology have long been underestimated. It has been demonstrated that PA lowers fatty acids content in liver and plasma, reduces food intake, exerts immunosuppressive actions and probably improves tissue insulin sensitivity. Thus increased production of PA by the microbiota might be considered beneficial in the context of prevention of obesity and diabetes type 2. The molecular mechanisms by which PA may exert this plethora of physiological effects are slowly being elucidated and include intestinal cyclooxygenase enzyme, the G-protein coupled receptors 41 and 43 and activation of the peroxisome proliferator-activated receptor γ, in turn inhibiting the sentinel transcription factor NF-κB and thus increasing the threshold for inflammatory responses in general. Taken together, PA emerges as a major mediator in the link between nutrition, gut microbiota and physiology.

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SCFA, especially propionate, can act as anti-inflammatory factors through interference in various inflammatory pathways.
“SCFA, especially propionate, can plays as anti-inflammatory factors through interference in various inflammatory pathways [87].”
From Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: systematic review and a dose-response meta-analysis of randomized controlled trials (2021) · cites this paper as [87]
Propionic acid is used as a preservative in the food industry and can induce autistic-like behaviors in rodents.
“In fact, higher levels of AA and PPA that is used as a preservative in the food industry and can also induce autistic-like behaviors in rodents have been reported in ASD children [177,178].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [177]
Higher levels of acetic acid and propionic acid have been reported in ASD children.
“In fact, higher levels of AA and PPA that is used as a preservative in the food industry and can also induce autistic-like behaviors in rodents have been reported in ASD children [177,178].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [177]

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The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism
den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D.-J., & Bakker, B. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r036012 · Cited by 5,048 · see citing works
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Short-Chain Fatty Acids Protect Against High-Fat Diet–Induced Obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation
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Short chain fatty acids in human gut and metabolic health
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Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity
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Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation
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The Gut Microbiome and the Brain
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The health benefits of dietary fiber: beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer
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Autism Spectrum Disorders and the Gut Microbiota
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Feeding the microbiota–gut–brain axis: Diet, microbiome, and neuropsychiatry
Sandhu, K. V., Sherwin, E., Schellekens, H., Stanton, C., Dinan, T. G., & Cryan, J. F. (2017) · Translational Research · doi:10.1016/j.trsl.2016.10.002 · Cited by 491 · see citing works
The Gut Microbiota and Autism Spectrum Disorders
Li, Q., Han, Y., Dy, A. B. C., & Hagerman, R. J. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00120 · Cited by 462 · see citing works
Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder
MacFabe, D. F., Cain, N. E., Boon, F., Ossenkopp, K.-P., & Cain, D. P. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.10.005 · Cited by 365 · see citing works
Adherence to the Mediterranean diet is associated with the gut microbiota pattern and gastrointestinal characteristics in an adult population
Mitsou, E. K., Kakali, A., Antonopoulou, S., Mountzouris, K. C., Yannakoulia, M., Panagiotakos, D. B., & Kyriacou, A. (2017) · British Journal of Nutrition · doi:10.1017/s0007114517001593 · Cited by 325 · see citing works
Enteric Bacterial Metabolites Propionic and Butyric Acid Modulate Gene Expression, Including CREB-Dependent Catecholaminergic Neurotransmission, in PC12 Cells - Possible Relevance to Autism Spectrum Disorders
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The Mediterranean dietary pattern as the diet of choice for non‐alcoholic fatty liver disease: Evidence and plausible mechanisms
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Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism
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Microbiome disturbances and autism spectrum disorders
Rosenfeld, C. S. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.063826 · Cited by 229 · see citing works
Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions
Ristori, M. V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., & Putignani, L. (2019) · Nutrients · doi:10.3390/nu11112812 · Cited by 214 · see citing works
Propionate. Anti-obesity and satiety enhancing factor?
Arora, T., Sharma, R., & Frost, G. (2011) · Appetite · doi:10.1016/j.appet.2011.01.016 · Cited by 205 · see citing works
Urinary p-cresol in autism spectrum disorder
Persico, A. M., & Napolioni, V. (2013) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2012.09.002 · Cited by 189 · see citing works
Probiotics: interaction with gut microbiome and antiobesity potential.
Arora, T., Singh, S., & Sharma, R. K. (2013) · Nutrition · doi:10.1016/j.nut.2012.07.017 · Cited by 176 · see citing works
Pathophysiological and neurobehavioral characteristics of a propionic acid-mediated autism-like rat model
Choi, J., Lee, S., Won, J., Jin, Y., Hong, Y., Hur, T.-Y., Kim, J.-H., Lee, S.-R., & Hong, Y. (2018) · PLOS ONE · doi:10.1371/journal.pone.0192925 · Cited by 139 · see citing works
Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines
Frye, R. E., Rose, S., Chacko, J., Wynne, R., Bennuri, S. C., Slattery, J. C., Tippett, M., Delhey, L., Melnyk, S., Kahler, S. G., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.189 · Cited by 130 · see citing works
NMR-based fecal metabolomics fingerprinting as predictors of earlier diagnosis in patients with colorectal cancer
Lin, Y., Ma, C., Liu, C., Wang, Z., Yang, J., Liu, X., Shen, Z., & Wu, R. (2016) · Oncotarget · doi:10.18632/oncotarget.8762 · Cited by 126 · see citing works
Sexually dimorphic effects of prenatal exposure to propionic acid and lipopolysaccharide on social behavior in neonatal, adolescent, and adult rats: Implications for autism spectrum disorders
Foley, K. A., MacFabe, D. F., Vaz, A., Ossenkopp, K., & Kavaliers, M. (2014) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2014.04.001 · Cited by 116 · see citing works
The microbiota and its metabolites in colonic mucosal health and cancer risk
Vipperla, K., & O'Keefe, S. J. (2012) · Nutrition in Clinical Practice · doi:10.1177/0884533612452012 · Cited by 116 · see citing works
Gut microbiota modulate the metabolism of brown adipose tissue in mice
Mestdagh, R., Dumas, M.-E., Rezzi, S., Kochhar, S., Holmes, E., Claus, S. P., & Nicholson, J. K. (2012) · Journal of Proteome Research · doi:10.1021/pr200938v · Cited by 97 · see citing works
Intestinal Barrier Dysfunction and Microbiota–Gut–Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder
Dargenio, V. N., Dargenio, C., Castellaneta, S., De Giacomo, A., Laguardia, M., Schettini, F., Francavilla, R., & Cristofori, F. (2023) · Nutrients · doi:10.3390/nu15071620 · Cited by 98 · see citing works
Effect of Flaxseed Intervention on Inflammatory Marker C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Ren, G.-Y., Chen, C.-Y., Chen, G.-C., Chen, W.-G., Pan, A., Pan, C.-W., Zhang, Y.-H., Qin, L.-Q., & Chen, L.-H. (2016) · Nutrients · doi:10.3390/nu8030136 · Cited by 88 · see citing works
An aPPARent functional consequence in skeletal muscle physiology via peroxisome proliferator-activated receptors
Phua, W. W. T., Wong, M. X. Y., Liao, Z., & Tan, N. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051425 · Cited by 72 · see citing works
<sup>1</sup>H NMR‐based metabolomics reveal overlapping discriminatory metabolites and metabolic pathway disturbances between colorectal tumor tissues and fecal samples
Lin, Y., Ma, C., Bezabeh, T., Wang, Z., Liang, J., Huang, Y., Zhao, J., Liu, X., Ye, W., Tang, W., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32190 · Cited by 57 · see citing works
Effects of Flaxseed Interventions on Circulating Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Rahimlou, M., Jahromi, N. B., Hasanyani, N., & Ahmadi, A. R. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz048 · Cited by 52 · see citing works
Intravenous administration of sodium propionate induces antidepressant or prodepressant effect in a dose dependent manner
Hao, C., Gao, Z., Liu, X., Rong, Z., Jia, J., Kang, K., Guo, W., & Li, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-77085-z · Cited by 43 · see citing works
Gut mechanisms linking intestinal sweet sensing to glycemic control
Kreuch, D., Keating, D. J., Wu, T., Horowitz, M., Rayner, C. K., & Young, R. L. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00741 · Cited by 40 · see citing works
Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: systematic review and a dose-response meta-analysis of randomized controlled trials
Yang, C., Xia, H., Wan, M., Lu, Y., Xu, D., Yang, X., Yang, L., & Sun, G. (2021) · Nutrition & Metabolism · doi:10.1186/s12986-021-00619-3 · Cited by 40 · see citing works
Are nonnutritive sweeteners obesogenic? Associations between diet, faecal microbiota, and short-chain fatty acids in morbidly obese subjects
Farup, P. G., Lydersen, S., & Valeur, J. (2019) · Journal of Obesity · doi:10.1155/2019/4608315 · Cited by 29 · see citing works
Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism
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Butyric acid and pivaloyloxymethyl butyrate, AN-9, a novel butyric acid derivative, induce apoptosis in HL-60 cells
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Authors: Al-Lahham, S. H., Peppelenbosch, M. P., Roelofsen, H., Vonk, R. J., & Venema, K.
Affiliations: Erasmus MC (NL)
University Medical Center Groningen (NL)
Corresponding author: Venema, Koen
ORCID: Peppelenbosch, Maikel P.
Vonk, Roel J.
Venema, Koen
Venue: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Publisher: Elsevier BV
Published: 2010-11
Volume: 1801
Issue: 11
Pages: 1175-1183
ISSN: 1388-1981 (ISSN-L)
DOI: 10.1016/j.bbalip.2010.07.007
OpenAlex: W2014444288
Cited by: 614
References: 132
Citations by year: 2026: 19 · 2025: 36 · 2024: 55 · 2023: 49 · 2022: 61 · 2021: 66 · 2020: 55 · 2019: 42 · 2018: 33 · 2017: 34 · 2016: 35 · 2015: 27 · 2014: 37 · 2013: 28 · 2012: 17
FWCI: 1.82
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
TNO Repository (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: propionic acid, short-chain fatty acids, gut microbiota, colonic fermentation, obesity, type 2 diabetes, insulin sensitivity, dietary intake, immunosuppression, PPARγ, NF-κB, adipokines, adipose tissue, cyclooxygenase, inflammation
MeSH terms: Adipose Tissue, Animals, Child, Child Development Disorders, Pervasive, Colon, Diabetes Mellitus, Type 2, Digestion, Fatty Acids, Humans, Insulin, Obesity, Propionates, NF-kappa B, Receptors, G-Protein-Coupled, PPAR gamma, Mice, Rats

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Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms

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