Friday, 02 December 2016 18:51

High-Fat Holiday Food and the Yo-Yo diet: Are microbes to blame for your weight re-gain?

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Published in Microbial Sciences

By Monika Buczek and Jennifer Brubaker

The holiday season is upon us, and we all know what that means: any progress made toward that perfect beach bod over the summer months comes crashing down in the face of Thanksgiving leftovers. You triumphantly lose five pounds in two days, only to gain it all back with an equally triumphant serving (or two, or three) of dessert. What gives?

We already know that diet affects the composition of microbes in our bodies (and our microbes affect our dietary restrictions as well); geneticists have chronicled nourishment and microbial composition all the way back to breastfeeding and human milk prebiotics. But it turns out that microbial ecology could have an important influence on our ability to keep weight off, as well. Immunologists at the Weizmann Institute of Science have discovered an “intestinal microbiome signature” that persists even after successfully dieting. This signature is responsible for changes in host physiology and aberrant metabolic responses when exposed to “obesity promoting conditions” (aka that piece of pumpkin cheesecake, or those buttery mashed potatoes). By tracing this signature, they’ve found that even after successfully taking off the pounds via diet, a return to fat-rich food can lead to increased weight gain and glucose intolerance nonetheless.

Think of it this way: just like that extra “belly pooch” takes up residence on the outside of our gut after repetitive intake of high-fat foods, our pre-diet host microbiota takes up long-term territory on the inside-- even when we make healthy changes and appear to become “fit” on the outside.

Changes to microbiota - Are they permanent or temporary?

To generate a “mouse model of recurrent obesity,” researchers introduced fluctuations in dietary fat content in mice by interleaving cycles of high-fat and low fat diet and subsequently measuring total body fat changes, glucose intolerance, leptin serum levels, LDL, and HDL. They found that mice with recurrent exposure to the high-fat diet exhibited dyslipidemia (high blood cholesterol or triglycerides), greater weight gain, and greater metabolic disturbances than control mice. After targeting the 16S locus for amplicon sequencing, scientists found that bacterial composition was also significantly different. Bacterial alpha-diversity was reduced and did not recover when the mice returned to normal weight. Furthermore, only 45% of all taxa returned to pre-obesity levels after dieting. Even after returning to a normal weight, the mice retained over half of the microbial composition that they had while obese. 

As far as long-term weight gain and deleterious metabolic repercussions, however, there were some reassuring observations (for individuals hoping to preserve their newfound health). In long-term testing of mice that returned to a normal weight researchers observed that fat content, serum cholesterol, glucose tolerance, and serum insulin remained consistent with pre-obesity levels. This suggests that as long as low-fat diet is adhered to, the persistence of obesity microbiota can at least be managed.

Unfortunately the same cannot be said for long-term microbial composition. Microbiota of mice on the high-fat diet showed detectable changes in 773 bacterial genes (identified via shotgun metagenomic sequencing) and their “functional pathways” and did not return to baseline when the mouse returned to normal weight.

In addition, fecal microbiome transplantation from post-diet mice passed metabolic derangement and glucose intolerance to control mice. All in all, microbiome configuration changed after weight gain and stayed that way even after loss. Specific studies of fecal metabolomics profiles indicated that high-fat diets lead to major changes, and these changes tend to persist for quite some time.

Among those changes include the reduction of two flavonoids after exposure to a high fat diet: apigenin and naringenin. Energy expenditure of post-diet mice (adjusted for weight) was markedly reduced compared to control mice who had never been obese, however, when these two flavonoids were administered to the weight-cycling mice, their energy expenditure returned to normal. Thus, flavonoid administration may be a useful therapeutic in returning post-diet energy expenditures to normal levels.

In order to characterize the role of flavonoids in host energy expenditure, scientists looked at the gene Ucp1, or uncoupling protein-1, which is involved in thermogenesis via brown adipose fat. Expression of Ucp1 was analyzed in normal and high-fat diet mice who also received flavonoids. Results showed Ucp1 was significantly higher in the brown adipose tissue of mice fed a high-fat diet AND flavonoids when compared with normal chow. Ucp1 expression was elevated in weight-cycling mice fed flavonoids, as well. This suggests that flavonoids actively increase energy expenditure by increasing levels of the UCP-1 protein, stimulating thermogenesis.

What we all really want to know: can you cultivate a healthy microbiome if you’ve already yo-yo dieted?

Obviously, there is a causal connection between the microbiome and weight regain, but what would happen if you wiped the slate clean and started all over again? The researchers tested this also. Treating with antibiotics after weight loss eventually lead to recolonization of normal pre-obesity microbiota. Further, and more notably, antibiotic treatment also removed the metabolic derangements seen in post-diet mice who were re-exposed to a high-fat diet. Though these results may appear to point to a potential obesity therapy, by no means does this mean you should wipe out your entire microbiome with antibiotics in search of a slimmer waistline. Antibiotic over-use has also been linked to obesity by altering the natural gut microbiome composition in other ways.

Aside from full nuclear warfare on your insides via antibiotics, this research has pointed to two very promising therapies for weight-loss: fecal microbiome transplantation and metabolite based treatment.

Fecal microbiome transplantation (FMT) in animal models has shown a positive correlation with decreasing propensity for weight re-gain, especially when transferred from individuals who have been fasting. Still in clinical trials by the FDA, this therapy may be available to human patients soon.

Metabolite-based treatment, including flavonoids (apigenin and naringenin). Flavonoid-based “post-biotic” treatment might help reduce weight re-gain after dieting. Apigenin and Naringenin metabolite therapies and could potentially modulate physiological function despite microbiome composition. Decreasing these two metabolites amplifies susceptibility for post-diet weight regain, and re-introducing them into diet may increase energy expenditure and reduce metabolic abnormalities.

But... what about exercise?

Does increased exercise help us evade the deleterious effects of weight-cycling phenomena? Unfortunately, we may not have such conscious control of our waistlines. In twin studies, dieting twins had a much more difficult time with weight regulation than non-dieting twins, independent of both exercise and initial weight.

Biomedical relevance

The microbiome is deeply involved in many health issues such as, but not limited to, Crohn’s disease, skin ulcers, acne, diabetes, inflammatory bowel disease, C. difficile gastroenteritis, and last but certainly not least, obesity. More than two-thirds of adults are considered to be overweight or obese in the United States, owing to inactivity, diet, and complex biological and socioeconomic factors. And it’s not for lack of trying—some people will attempt anything to decrease their BMI including binge drinking, tapeworms, and stimulant abuse.

If our gut microbiota are in fact causal in weight gain, therapies that target the microbiome could have powerful and long-awaited results for struggling patients. Until then, keep your microbes in mind during the delicious fatty food filled holidays.

Further reading:

Neumark-Sztainer, D. et al. (2006). Obesity, disordered eating, and eating disorders in

a longitudinal study of adolescents: how do dieters fare 5 years later? J Am Diet Assoc 106, 559–568. doi:10.1016/j.jada.2006.01.003

Ravel J et al. (2013). Human microbiome science: vision for the future, Bethesda, MD, July 24 to 26, 2013. Microbiome, 2:16. http://microbiomejournal.biomedcentral.com/articles/10.1186/2049-2618-2-16

Saarni SE et al. (2006). Weight cycling of athletes and subsequent weight gain in middle age. Int J Obes (Lond) 30, 1639–1644. doi:10.1038/sj.ijo.0803325

Thaiss CA, et al. (2016). Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature. Accelerated press. http://dx.doi.org/10.1038/nature20796.

 

Jennifer Brubaker is a medical student at Ohio University Heritage College of Osteopathic Medicine. She received her graduate degree Jennifer Brubakerfrom Johns Hopkins University in Biotechnology, where she studied Human Molecular Genetics and Emerging Infectious Diseases. She graduated from Boston College with a degree in Biology in 2012.

 

Last modified on Friday, 02 December 2016 21:46
Monika Buczek

Monika Buczek is a Ph.D. candidate in the Molecular, Cellular and Developmental Biology Department at the City University of New York Graduate Center. She is a member of Dr. Anu­rad­ha Janakiraman's lab at the CCNY Center for Discovery and Innovation, and her thesis research focuses on the proteolytic regulation of E.coli cytokinesis. She also teaches as an adjunct lecturer in Molecular Biology and Microbiology at the City College of New York. 

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