Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
Open accessAbstract
Transforming Fat to Thin: How much does the microbiota influence the host's phenotype? Ridaura et al. ( 1241214 ; see the Perspective by Walker and Parkhill ) obtained uncultured fecal microbiota from twin pairs discordant for body mass and transplanted them into adult germ-free mice. It was discovered that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Moreover, obese-phenotype mice were invaded by members of the Bacteroidales from the lean mice, but, happily, the lean animals resisted invasion by the obese microbiota.
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The energy extraction difference is thought to be driven by an expansion in pro-inflammatory species of bacteria, such as E. coli, and a depletion of anti-inflammatory bacteria such as Faecalibacterium prausnitzii.
“This is thought to be driven by an expansion in pro-inflammatory species of bacteria, such as E. coli, and a depletion of anti-inflammatory bacteria such as Faecalibacterium prausnitzii [133,134].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [133]
The sections on functional differences between transplanted communities and changes in the cecal metabolome discuss bacterial composition, metabolites, and host energy balance. Searches for E. coli, Faecalibacterium prausnitzii, and the proposed pro- versus anti-inflammatory mechanism found no passage in our copy that addresses the claimed explanation for an energy-extraction difference. (LLM, conf=0.72)
Experimental — accuracy not yet measuredAthletes have an enriched profile of SCFAs, previously associated with numerous health benefits and a lean phenotype.
“Furthermore, athletes have an enriched profile of SCFAs, previously associated with numerous health benefits and a lean phenotype.[33][34][35]”
From The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level (2018) · cites this paper as [34]
The same clusters are observed when correlating with individual taxa, in support of previously observed links between SCFAs and numerous metabolic benefits and a lean phenotype.
“The same clusters are observed when correlating with individual taxa, in support of previously observed links between SCFAs and numerous metabolic benefits and a lean phenotype.[33][34][35]”
From The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level (2018) · cites this paper as [34]
Studies with gnotobiotic mice colonized with the microbiota of lean or obese twins have shown that this phenotype is transmissible.
“Studies with gnotobiotic mice colonized with the microbiota of lean or obese twins have also shown that this phenotype is also transmissible [7].”
From Intestinal Microbiota Is Influenced by Gender and Body Mass Index (2016) · cites this paper as [7]
The same weight-increasing effect is observed when microbiota from obese or lean humans is transferred to germ-free mice.
“This observation also holds true when the microbiota from obese or lean humans is transferred to germ-free mice (Ridaura et al., 2013; Tremaroli et al., 2015).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Ridaura et al., 2013
Altering the gut microbiome in humans and mice has shown improvement in metabolic syndrome.
“altering the gut microbiome in humans and mice has shown improvement in metabolic syndrome.”
From The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids (2015) · cites this paper as [14]
Microbiota alterations in obese humans can confer obese or adiposity phenotypes when transferred to mice.
“reports of alterations in the gut microbiota of obese people4,13–15, which confer the obese or adiposity phenotypes when transferred to mice14,16”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [14]
In mice, a lean microbiota could colonize and protect against fat gain only if the animals ate a low-fat diet rich in fruits and vegetables.
“Importantly, the lean microbiota could only invade and prevent increased adiposity when the recipient mice consumed a diet that was low in fat and high in fruits and vegetables.”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [14]
Bacteria from lean individuals were linked to greater short-chain fatty acid production.
“bacterial representatives from the microbiota of lean individuals were associated with an increased production of short-chain fatty acids”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [14]
The microbiota of obese people had more genes for making branched-chain amino acids, and these genes correlate with poorer insulin sensitivity.
“the microbiota of obese individuals had an increased abundance of genes that are involved in biosynthesis of branched-chain amino acids, which are associated with impaired sensitivity to insulin14.”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [14]
Transferring gut microbiota from lean and obese individuals to ex-germ-free mice can reproduce the metabolic phenotype.
“Transfer of gut microbiota from lean and obese individuals can recapitulate the metabolic phenotype in ex-germ free mice.14”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [14]
Multiple evidence streams indicate that gut microbes contribute to obesity.
“Several lines of evidence support the role of gut microbiota in obesity.”
From Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook (2015) · cites this paper as [14]
Multiple human and animal studies have linked increased branched-chain amino acids with insulin resistance and type 2 diabetes in obese groups.
“Multiple human and animal studies have linked increased branched-chain amino acids (BCAAs) with insulin resistance and type 2 diabetes in obese groups [150,151,152,153].”
From Impact of Protein Intake in Older Adults with Sarcopenia and Obesity: A Gut Microbiota Perspective (2020) · cites this paper as [151]
Obesity can be transferred from obese mice or humans to healthy mice via conventionalization.
“experiments have shown that the condition can be transferred from obese mice or humans to healthy mice via conventionalization (i.e. microbiota transfer by feeding fecal material) [64, 65].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [65]
The gut microbiota plays a key role in the pathogenesis of obesity.
“Gut microbiota plays a key role in the pathogenesis of obesity.”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [65]
Athletes have an enriched profile of short-chain fatty acids, previously associated with numerous health benefits and a lean phenotype.
“Furthermore, athletes have an enriched profile of SCFAs, previously associated with numerous health benefits and a lean phenotype [61–63].”
From The athletic gut microbiota (2020) · cites this paper as [63]
Obese mice fed a low saturated fat, high fruit and vegetable diet can take on microbiota characteristics of lean mice.
“obese mice fed a low saturated fat, high fruit and vegetable diet can take on microbiota characteristics of lean mice [63].”
From The athletic gut microbiota (2020) · cites this paper as [63]
Mice consuming a low saturated fat, high fruit and vegetable diet gained less fat mass than mice fed a high-saturated fat, low fruit and vegetable Westernized diet, regardless of lean or obese state.
“mice consuming this diet regardless of lean or obese state gained less fat mass compared to lean and obese mice fed a high-saturated fat, low fruit and vegetable diet, typical of a Westernized diet.”
From The athletic gut microbiota (2020) · cites this paper as [63]
SCFAs are linked to numerous metabolic benefits and a lean phenotype.
“in support of purported links between SCFAs and numerous metabolic benefits and a lean phenotype [61–63].”
From The athletic gut microbiota (2020) · cites this paper as [63]
Transplantation of fecal microbiota from patients with obesity, steatosis or type 2 diabetes can partly reproduce the donor's metabolic phenotype in mouse recipients.
“transplantation of the fecal microbiota from patients with obesity, steatosis or type 2 diabetes can partly reproduce the donor’s metabolic phenotype in mouse recipients [4–7].”
From Dietary lipids, gut microbiota and lipid metabolism (2019) · cites this paper as [4]
Human and animal studies have established the ability to successfully populate the oral cavity or gastrointestinal tract with specific strains, combinations of bacteria, or bacteria genetically modified to produce enzymes or metabolites.
“While human and animal studies have established the ability to successfully populate the oral cavity or gastrointestinal tract with specific strains, combinations of bacteria, or bacteria genetically modified to produce enzymes or metabolites[74,404–407]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [404]
Transplantation of the microbiome from the obese but not normal-weight twin to healthy germ-free mice promotes adiposity and perturbs glucose metabolism.
“similar transplantation of the microbiome from the obese but not normal-weight twin, to healthy germ-free mice, also promotes adiposity and perturbs glucose metabolism [9].”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [9]
Transplanting the microbiota of genetically obese ob/ob mice or obese humans to lean germfree mice increases the adiposity of the recipient mice.
“transplanting the microbiota of genetically obese ob/ob mice or obese humans to lean germfree mice increases the adiposity of the recipient mice [8], [9]”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [9]
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Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders
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The role of the microbiome in NAFLD and NASH
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Human genetic variation and the gut microbiome in disease
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Persistent microbiome alterations modulate the rate of post-dieting weight regain
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Sex, body mass index, and dietary fiber intake influence the human gut microbiome
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Gut microbiota: A player in aging and a target for anti-aging intervention
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The gut microbiota in human energy homeostasis and obesity
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Dietary effects on human gut microbiome diversity
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Role of the gut microbiota in type 2 diabetes and related diseases
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Weight Gain After Fecal Microbiota Transplantation
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- Authors
- Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., Griffin, N. W., Lombard, V., Henrissat, B., Bain, J. R., Muehlbauer, M. J., Ilkayeva, O., Semenkovich, C. F., Funai, K., Hayashi, D. K., Lyle, B. J., Martini, M. C., Ursell, L. K., Clemente, J. C., Van Treuren, W., Walters, W. A., Knight, R., Newgard, C. B., Heath, A. C., & Gordon, J. I.
- Affiliations
- Washington University in St. Louis (US)
- Centre National de la Recherche Scientifique (FR)
- University of Copenhagen (DK)
- Duke Medical Center (US)
- Mondelēz International (United States) (US)
- Kraft Foods Group, Glenview, IL 60025, USA.
- University of Colorado Boulder (US)
- Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
- Howard Hughes Medical Institute (US)
- Corresponding author
- Gordon, Jeffrey I.
- ORCID
- Ridaura, Vanessa K.
- Faith, Jeremiah J.
- Rey, Federico E.
- Cheng, Jiye
- Duncan, Alexis E.
- Kau, Andrew L.
- Griffin, Nicholas W.
- Lombard, Vincent
- Henrissat, Bernard
- Bain, James R.
- Muehlbauer, Michael J.
- Ilkayeva, Olga
- Semenkovich, Clay F.
- Funai, Katsuhiko
- Lyle, Barbara J.
- Walters, William A.
- Knight, Rob
- Newgard, Christopher B.
- Heath, Andrew C.
- Gordon, Jeffrey I.
- Venue
- Science
- Published
- 2013-09-06
- Volume
- 341
- Issue
- 6150
- Pages
- 1241214-1241214
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3829625
- OpenAlex
- W1993399595
- Cited by
- 3,788
- References
- 76
- Citations by year
- 2026: 169 · 2025: 209 · 2024: 260 · 2023: 289 · 2022: 329 · 2021: 422 · 2020: 387 · 2019: 322 · 2018: 357 · 2017: 306 · 2016: 267 · 2015: 264 · 2014: 174 · 2013: 29 · 2012: 1
- FWCI
- 109.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Crohn's and Colitis Foundation
- National Institute on Alcohol Abuse and Alcoholism (K05AA017688)
- National Institute on Aging (P30AG028716)
- National Institute of General Medical Sciences (T32GM008759, T32GM142607)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK095774, P01DK058398, DK078669, DK-58398, P01DK078669, R01DK076729, DK 70977, F32DK091044, R01DK070977, P30DK056341, P30DK020579)
- 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, twin discordance, fecal microbiota transplantation, germ-free mice, body composition, fat mass, Bacteroidetes, diet-microbiome interactions, saturated fat, fruit and vegetable intake, metabolic phenotypes
- MeSH terms
- Adult, Animals, Cecum, Feces, Female, Germ-Free Life, Humans, Mice, Inbred C57BL, Mice, Obese, Obesity, Thinness, Twins, Weight Gain, Diet, Fat-Restricted, Bacteroidetes, Gastrointestinal Tract, Adiposity, Mice, Metagenome, Metabolome, Young Adult
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