The gut microbiota, obesity and insulin resistance
Abstract
The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate fundamental discoveries in energy metabolism, molecular endocrinology and immunobiology and may lead to new strategies for prevention of obesity and its complications.
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The gut microbiota influences host energy metabolism and gut barrier integrity.
“In addition to the effects on immune function, the gut microbiota also exerts its role through the influence on host energy metabolism and gut barrier integrity [10,11].”
From Effects of Regular Kefir Consumption on Gut Microbiota in Patients with Metabolic Syndrome: A Parallel-Group, Randomized, Controlled Study (2019) · cites this paper as [10]
Acetate, propionate, and butyrate can preferentially activate free fatty acid receptors (FFARs) to increase energy harvest and triglyceride storage in adipose tissue.
“Molecular data showed that acetate, propionate, and butyrate can preferentially activate a series of free fatty acid receptors (FFARs) to increase energy harvest and triglyceride storage in adipose tissue [34,35,36].”
From Preventive Effects and Mechanisms of Garlic on Dyslipidemia and Gut Microbiome Dysbiosis (2019) · cites this paper as [36]
The result has been the development of a mismatch between human metabolic genes and bacteria that enhance fat storage.
“The result has been the development of a mismatch between human metabolic genes and bacteria that enhance fat storage [128].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [128]
In our evolutionary past, when nutrients were scarce, host selection led to the maintenance of microbes that enhance nutrient uptake or host energy storage.
“In our evolutionary past, when nutrients were scarce, it has been theorized that host selection led to the maintenance of microbes that enhance nutrient uptake or host energy storage.”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [128]
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- Authors
- Shen, J., Obin, M. S., & Zhao, L.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Tufts University (US)
- Corresponding author
- Zhao, Liping
- Venue
- Molecular Aspects of Medicine
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 34
- Issue
- 1
- Pages
- 39-58
- ISSN
- 0098-2997 (ISSN-L)
- OpenAlex
- W2137068383
- Cited by
- 599
- References
- 29
- Citations by year
- 2026: 10 · 2025: 32 · 2024: 21 · 2023: 44 · 2022: 68 · 2021: 54 · 2020: 51 · 2019: 53 · 2018: 47 · 2017: 48 · 2016: 55 · 2015: 52 · 2014: 40 · 2013: 23
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Aspects of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, obesity, insulin resistance, metabolic endotoxemia, intestinal permeability, bacterial translocation, dysbiosis, host-microbe crosstalk, energy metabolism, energy expenditure, fat deposition, dietary habits, prebiotics, probiotics, obesity-associated inflammation
- MeSH terms
- Animals, Energy Intake, Energy Metabolism, Humans, Inflammation, Insulin Resistance, Obesity, Thinness, Endotoxemia, Probiotics, Gastrointestinal Tract, Mice, Metagenome, Prebiotics
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