Microbes Make Some Folks Fat
Human/mouse study links gut bacteria to weight gain and metabolic disorders
Human/mouse study links gut bacteria to weight gain and metabolic disorders
The stream of evidence linking human health to intestinal microbes is fast growing into a flood.
Your gut hosts trillions of microbes – a population called the “microbiome” or “microflora” – that help break down (metabolize) food and make nutrients.
And it's become clear that our microbial colonies play critical roles in health, with doctors now curing people by transferring microbe-rich tissues or waste from healthy people into sick ones.
Typically, the transferred material is implanted into the corresponding organ, such as the nose of someone with sinusitis, or the colon of a person with intestinal problems.
Soon, they may be doing it to help cure obesity.
Intestinal microbiomes can determine health destiny
Earlier this year, Scientists at Washington University in St. Louis found that some African children are malnourished because their mix of gut microbes.
This was discovered by studying twins with near-identical genomes and diets, whose microbial eco-systems nonetheless differed from their twin sibling's.
Having an unhealthful microbiome altered a child's food metabolism and disrupted a central metabolic pathway for extracting energy from food.
And mice implanted with gut microbes from a malnourished twin carried species of bacteria associated with human illnesses, including inflammatory bowel disease (WUSL 1/30/2013).
What are probiotics?
Probiotics are bacteria that help maintain a healthful balance of microbes (microflora) in the intestines, and generally benefit their host.
The average person's digestive tract hosts about 400 kinds of probiotic bacteria, which help prevent the growth of harmful bacteria and promote healthy digestion.
Lactic acid bacteria – such as L. acidophilus and other lactobacillus – are the largest single class of probiotics in a normal, healthy human digestive tract.
Lactobacillus are often given to patients following a course of antibiotics, and are also found in yogurt and most other cultured/fermented foods.
In 2009, a study by the Washington University team indicated that the mix of microbes in the guts of obese people lack the diversity and richness of people who are lean.
This observation was confirmed by a recent Danish clinical study that linked the risk for metabolic disorders – obesity, cardiovascular disease, and diabetes – to a shortage of friendly intestinal bacteria.
And the Danes found that the microbiomes of bacteria-poor people were dominated by species that cause chronic inflammation in the body (Le Chatelier E et al. 2013).
Now, a clever study testing human gut bugs in mice affirms the link between our microbiomes and the risk of weight gain and related metabolic problems.
Mice given human gut microbes point to possible obesity cure
Scientists at Washington University in St. Louis report a breakthrough in understanding obesity … which many lead to a novel therapy (Ridaura VK et al. 2013).
According to senior author Jeffrey Gordon, M.D., “Our results underscore the strong interactions between gut microbes and diet and help illustrate how unhealthy diets select against gut microbes associated with leanness.” (WUSL 9/5/2013)
The researchers took gut microbes from pairs of human female adult twins (identical and fraternal), among whom one twin was obese and the other was lean … a disparity seen in about six percent of twins.
Gut microbes from the lean and obese human twins were transferred into mice that had been raised in a previously microbe-free environment.
The study had two separate phases:
Phase I – Transfer human microbes into mice
First, the researchers transplanted microbes from the lean and obese human twins into mice lacking intestinal microbes.
All of the mice were fed a low-fat mouse chow, with these results:
Mice given “lean microbes” stayed lean and healthy.
Mice given “obesity microbes” gained weight and displayed the donor's metabolic dysfunctions, such as insulin resistance.
Phase II – Test the interactions between diet and gut microbes
For the second phase of the study, mice implanted with lean-twin microbes were put in cages with mice carrying obesity microbes.
The mice carrying obesity microbes were divided into two groups, based on their diet:
- Healthy human diet, low in saturated fat and high in fruits and vegetables.
- Unhealthy human diet, high in saturated fat and low in fruits and vegetables.
Mice naturally eat each other's droppings, so the researchers could see what happened when a mouse carrying obesity microbes ate feces from a mouse carrying lean microbes.
Would lean microbes consumed by mice hosting an obesity microbiome become dominant and make those mice lean?
Critically, the results showed that the answer depended on diet.
In short, changing the microbial mix and diet in mice otherwise destined for obesity and metabolic problems saved them from that fate:
- Lean microbes took hold in mice fed a healthy diet, which prevented weight and metabolic problems.
- Lean microbes did not take hold in mice fed an unhealthful diet, and the animals proceeded to gain weight and fat and develop metabolic problems.
The results greatly strengthen the case that interactions between gut microbes and diet are essential factors in causing and maintaining obesity (Ridaura VK et al. 2013).
Some of the benefits seen in the obese mice eating healthy diets were attributed to microbes called Bacteroidetes, which extract calories and nutrients from food efficiently, and are linked to leanness.
Hopefully, the findings may set the stage for targeted “probiotic” supplements and foods designed to treat or prevent obesity.
The research was funded by the National Institutes of Health (NIH), the Crohn's and Colitis Foundation of America, Kraft Foods, and Mondelez International.
- Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008 Jun;57(6):1470-81. doi: 10.2337/db07-1403. Epub 2008 Feb 27.
- Cotillard A et al. Dietary intervention impact on gut microbial gene richness. Nature 500, 541–546 (29 August 2013) doi:10.1038/nature12506. Received 10 April 2012 Accepted 26 July 2013 Published online 28 August 2013
- Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Neyrinck AM, Possemiers S, Van Holle A, François P, de Vos WM, Delzenne NM, Schrenzel J, Cani PD. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes. 2011 Nov;60(11):2775-86. doi: 10.2337/db11-0227. Epub 2011 Sep 20. Erratum in: Diabetes. 2011 Dec;60(12):3307.
- Muccioli, Giulio M [corrected to Muccioli, Giulio G]. Kemperman A, Gross G, Mondot S. et al. Impact of polyphenols from black tea and red wine/grape juice on a gut model microbiome. Food Research International. Volume 53, Issue 2, October 2013, Pages 659–669. doi: 10.1016/j.foodres.2013.01.034
- Le Chatelier E et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (29 August 2013) doi:10.1038/nature12506. Received 10 April 2012 Accepted 26 July 2013 Published online 28 August 2013
- Pedersen R, Andersen AD, Mølbak L, Stagsted J, Boye M. Changes in the gut microbiota of cloned and non-cloned control pigs during development of obesity: gut microbiota during development of obesity in cloned pigs. BMC Microbiol. 2013 Feb 7;13:30. doi: 10.1186/1471-2180-13-30
- Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013 Sep 6;341(6150):1241214. doi: 10.1126/science.1241214.
- Tilg H. Obesity, metabolic syndrome, and microbiota: multiple interactions. J Clin Gastroenterol. 2010 Sep;44 Suppl 1:S16-8. doi: 10.1097/MCG.0b013e3181dd8b64.
- van Dorsten FA, Grün CH, van Velzen EJ, Jacobs DM, Draijer R, van Duynhoven JP. The metabolic fate of red wine and grape juice polyphenols in humans assessed by metabolomics. Mol Nutr Food Res. 2010 Jul;54(7):897-908. doi: 10.1002/mnfr.200900212.
- van Dorsten FA, Peters S, Gross G, Gomez-Roldan V, Klinkenberg M, de Vos RC, Vaughan EE, van Duynhoven JP, Possemiers S, van de Wiele T, Jacobs DM. Gut microbial metabolism of polyphenols from black tea and red wine/grape juice is source-specific and colon-region dependent. J Agric Food Chem. 2012 Nov 14;60(45):11331-42. doi: 10.1021/jf303165w. Epub 2012 Nov 1.
- van Duynhoven J, Vaughan EE, Jacobs DM, Kemperman RA, van Velzen EJ, Gross G, Roger LC, Possemiers S, Smilde AK, Doré J, Westerhuis JA, Van de Wiele T. Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4531-8. doi: 10.1073/pnas.1000098107. Epub 2010 Jun 25
- Washington University in St. Louis (WUSL) / Arbanas C. Gut microbes at root of severe malnutrition in kids. January 30, 2013. Accessed at https://news.wustl.edu/news/Pages/24874.aspx
- Washington University in St. Louis (WUSL) / Arbanas C. Altering mix of gut microbes prevents obesity, but diet remains key factor. September 5, 2013. Accessed at https://news.wustl.edu/news/Pages/25786.aspx