Oh my microbiome: why do you do this to me?
The impact of the gut microbiome on weight gain
How many of us have gained weight in the past and decided that we did not like what we were seeing or perhaps that our weight was unhealthy? And, having seen our expanded waistlines, rear ends or what-have-yous, determined to do something about it? I have written recently about unhealthy weight gain and diabetes and what we might do about it. Having made our realization, we make the effort to resume our former, slimmer figures and lose weight through diet and exercise over the course of weeks or months. It isn’t easy, but we keep on trying and often achieve success. Or do we? After all that effort, many of us slowly regain the weight that we had lost and often even a little extra. In fact, some of us cycle through periods of weight loss and subsequent regain. This is really not fair.
I have a simple question, dear reader – why does this happen and how might we prevent it?
Perhaps an answer, or at least a partial answer, is starting to emerge. The result may surprise you. Something very, very small seems to be impacting our health in unexpected ways.
Recent research published in Nature by scientists at the Weizmann Institute of Science in Israel may have revealed at least part of the answer. Do we regain weight because of lack of will power? Is it because of mental health issues? Are some of us just meant to be overweight? It is, at least in part, due to the gut microbiome. Our personal collection of bacteria and other microorganisms living within us in our gut may play a significant part in yo-yo weight loss and regain.
In an extensive series of experiments in mice, Thaiss et al.1 identified an intestinal microbiome signature that is present before and after successful dieting of obese mice and even contributes to faster weight regain after successful dieting. This unfortunate ability to quickly regain weight was even ‘catching’ with previously germ-free mice showing accelerated weight regain following fecal transfer. They further identified metabolomic alterations that included reduced post-dieting flavonoid levels and lowered energy expenditure. Subsequent experiments to ‘treat’ the mice for their enhanced weight regain, where flavonoids were added to the mouse diet, did indeed result in reduced weight regain on a high-fat diet.
They used a unique metabolomics technology to measure the changes in metabolism. The platform is a combination of state-of-the-art liquid chromatography coupled to mass spectrometry (LC-MS) utilizing sophisticated informatics tools, which typically identifies approximately 1,000 metabolites in human samples based upon comparison to an extensive library of mass spectra (plus other information) created by Metabolon. This range of metabolites includes, of course, those produced by the host, but also those produced by bacteria that make up much of the gut microbiome.
Putting this into perspective, Nobel Prize winner Dr. Joshua Lederberg popularized the term microbiome at the turn of the century and defined it as “the ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our body space and have been all but ignored as determinants of health and disease.” The clear implication was that the microbiome likely did play a part in keeping us healthy. Today, there is a large and growing body of literature that demonstrates that changes to the human microbiome, known as dysbiosis, are involved in a plethora of illness such as type 2 diabetes, arthritis, asthma, autism, colon cancer, inflammatory bowel disease and more.
Indeed, the microbiome is a very ‘hot’ area of both research and investment, with a large number of biotech companies starting up in recent years to exploit microbiome research. The rate of investment by venture capital, for example, in the last several years has been far higher than the average rate of growth of venture capital funding.2
Taken together, the results in Thaiss et al. strongly suggest a role for the gut microbiome in post-dieting weight regain, but also suggest possible dietary solutions. However, we have to note that these were experiments on mice in the lab, so we have a way to go before we can be sure that these are of relevance to you and me. Nevertheless, this work is intriguing and clearly suggestive of how to proceed to lose weight and not regain it.
Sometimes the world seems like a pretty strange place, but at times that strange is some kind of wonderful.
To learn more about the microbiome, you can watch a TED talk by Rob Knight. If you would like to learn more about the role of metabolomics in microbiome research, Metabolon has produced a free eBook that you can download.
Metabolon is proud to be a Premier Sponsor of the 24th Molecular Medicine Tri-Con meeting to be held in San Francisco, February 19-24, 2017. You'll find us at Booth #435 during the MMTC main conference and Booth #109 during the MMTC symposia.
We’re also giving some presentations on metabolomics and the microbiome and invite you to join us if you’re at the conference.
Tuesday, February 21, 2017
PCR & NGS for Molecular Diagnostics session
3:40pm - 4:10pm PST
Constructing an Atlas of the Human Metabolome to Enable Phenotyping & Genome Mapping
Mike Milburn, Ph.D., Chief Science Officer, Metabolon
By producing a comprehensive read-out of an individual, we will describe how metabolomics is creating an “atlas” for understanding human health and disease and elucidating how major drivers like genetics, lifestyle and the microbiome exert their influence.
Thursday, February 23, 2017
Microbiome-Based Precision Medicine session
10:00am - 10:30am PST
The Essential Ingredients for Decoding the Microbiome with Metabolomics
Kirk Beebe, Ph.D., Director of Application Science, Metabolon
The microbiome has a vital role in health, but lack of mechanistic understanding hinders the practical use of this information. We will illustrate how, through surveying the metabolites that broker microbe-host interaction, metabolomics can enrich insights into this association.
Dr. Beebe will also be a panelist at the Charles River Microbiome Think Tank luncheon that day at 12:40pm PST.
1. Thaiss C.A. et al. Persistent microbiome alterations modulate the rate of post-dieting weight regain Nature 540, 544-551 (2016).
2. B. Gormley, ‘Microbiome Companies Attract Big Investments.’ Wall Street Journal published Sept 18, 2016.