Cultured gut microbiota from twins discordant for obesity modulate adiposity and metabolic phenotypes in mice

By Vanessa K. Ridaura, Jeremiah J. Faith, Federico E. Rey, Jiye Cheng, A. Duncan, A. L. Kau, Nicholas W. Griffin, Vincent Lombard, B. Henrissat, James R. Bain and 15 more. Science, 2013

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Introduction Establishing whether specific structural and functional configurations of a human gut microbiota are causally related to a given physiologic or disease phenotype is challenging. Twins discordant for obesity provide an opportunity to examine interrelations between obesity and its associated metabolic disorders, diet, and the gut microbiota. Transplanting the intact uncultured or cultured human fecal microbiota from each member of a discordant twin pair into separate groups of recipient germfree mice permits the donors’ communities to be replicated, differences between their properties to be identified, the impact of these differences on body composition and metabolic phenotypes to be discerned, and the effects of diet-by-microbiota interactions to be analyzed. In addition, cohousing coprophagic mice harboring transplanted microbiota from discordant pairs provides an opportunity to determine which bacterial taxa invade the gut communities of cage mates, how invasion correlates with host phenotypes, and how invasion and microbial niche are affected by human diets. Cohousing Ln and Ob mice prevents increased adiposity in Ob cage mates (Ob). (A) Adiposity change after 10 days of cohousing. *P < 0.05 versus Ob controls (Student’s t test). (B) Bacteroidales from Ln microbiota invade Ob microbiota. Columns show individual mice. Methods Separate groups of germfree mice were colonized with uncultured fecal microbiota from each member of four twin pairs discordant for obesity or with culture collections from an obese (Ob) or lean (Ln) co-twin. Animals were fed a mouse chow low in fat and rich in plant polysaccharides, or one of two diets reflecting the upper or lower tertiles of consumption of saturated fats and fruits and vegetables based on the U.S. National Health and Nutrition Examination Survey (NHANES). Ln or Ob mice were cohoused 5 days after colonization. Body composition changes were defined by quantitative magnetic resonance. Microbiota or microbiome structure, gene expression, and metabolism were assayed by 16S ribosomal RNA profiling, whole-community shotgun sequencing, RNA-sequencing, and mass spectrometry. Host gene expression and metabolism were also characterized. Results and Discussion The intact uncultured and culturable bacterial component of Ob co-twins’ fecal microbiota conveyed significantly greater increases in body mass and adiposity than those of Ln communities. Differences in body composition were correlated with differences in fermentation of short-chain fatty acids (increased in Ln), metabolism of branched-chain amino acids (increased in Ob), and microbial transformation of bile acid species (increased in Ln and correlated with down-regulation of host farnesoid X receptor signaling). Cohousing Ln and Ob mice prevented development of increased adiposity and body mass in Ob cage mates and transformed their microbiota’s metabolic profile to a leanlike state. Transformation correlated with invasion of members of Bacteroidales from Ln into Ob microbiota. Invasion and phenotypic rescue were diet-dependent and occurred with the diet representing the lower tertile of U.S. consumption of saturated fats, and upper tertile of fruits and vegetables, but not with the diet representing the upper tertile of saturated fats, and lower tertile of fruit and vegetable consumption. These results reveal that transmissible and modifiable interactions between diet and microbiota influence host biology. 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. Mice carrying gut bacteria from lean humans protect their cage mates from the effects of gut bacteria from fat humans. [Also see Perspective by Walker and Parkhill] The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin’s microbiota (Ob) with mice containing the lean co-twin’s microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/ab9c1a504ceaa76448437e18de02808c54ebe5e7

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Citations in the corpus

Starving our Microbial Self: The Deleterious Consequences of a Diet Deficient in Microbiota-Accessible Carbohydrates (2014, positive): “The contribution of the dysbiotic microbiota to disease phenotype has been illustrated via microbiota transplant in several instances (Koren et al., 2012; Liou et al., 2012; Ridaura et al., 2013; Turnbaugh et al., 2006; Vijay-Kumar et al., 2010).”
Effects of diurnal variation of gut microbes and high fat feeding on host circadian clock function and metabolism (2015, positive): “B) corroborating previous reports (Backhed et al., 2004; Carvhalo et al., 2012; Ridaura et al., 2013; Turnbaugh et al, 2006).”
Personalized Nutrition by Prediction of Glycemic Responses. (2015, positive): “…been associated with low levels of Roseburia inulinivorans (Qin et al., C 2012; Figure 6E), Eubacterium eligens (Karlsson et al., 2013), and Bacteroides vulgatus (Ridaura et al., 2013), and all these bacteria increase following the ‘‘good’’ diet and decrease following the ‘‘bad’’ diet (Figure 6C).”
Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut (2016, positive): “…provide evidence for cause-and-effect relationships between shifts in gut microbiota composition and certain disorders (as in the case of obesity; Ridaura et al., 2013), it has not been proven yet for humans whether changes in the gut microbiota composition can cause disorders or that these…”
Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences (2014, positive): “, 2010) and host species (humans and mice) (Ridaura et al., 2013).”
Human genetics shape the gut microbiome. (2014, neutral): “Transfer to germ-free mice of microbiomes from obese and lean donors generally results in greater adiposity gains for obese compared to lean donors (Ridaura et al., 2013; Turnbaugh et al., 2008; Vijay-Kumar et al., 2010).”
FEAST: fast expectation-maximization for microbial source tracking (2019, positive): “…that it has been linked to many aspects of human physiology and health including obesity, inflammatory diseases, cancer, metabolic diseases and aging 2–4 We showed the ability of FEAST to differentiate between the gut microbiome of ICU patients experiencing dysbiosis and that of healthy controls.”