Prof. Jack A Gilbert
Department of Surgery, University of Chicago
Author of ‘Dirt is Good: The advantage of germs for your child’s developing immune system’
A recent article in Forbes Magazine (“Will You Lose Weight? Take a Look at Your Poop,” by Bruce E. Lee, September 16. 2017) discusses the recent scientific revelation that our intestinal bacteria have a role to play in attempts at weight loss, so that even if two people maintain the same diet, their results may not be the same. This news serves to underline what we have known for some time, namely, that our understanding of the digestive system is tenuous and incomplete. The fact that counting calories is merely part of any diet, and there exist factors beyond our control, reminds us of the great mystery that surrounds human digestion. The concept of the microbiome and of the role bacteria play in the gut adds one more piece to an incomplete jigsaw puzzle.
As we now know, you are home to a veritable rainforest of microorganisms. Over 40 trillion bacteria, archaea, fungi, and viruses to whom you are just another environment in which to nestle into. We call this the microbiome, the microbial ecosystem of your body. They cover every facet of you; every surface that has a link to the outside has been colonized by over 1000 different species. Your body has even created a system to keep them in check. Your immune is like a gardener, fostering the growth of microbes that have a benefit for our health and wellbeing, and weeding out those that are undesirable for the host. However, this interaction is a two-way street.
As long as the immune-microbiome balance is maintained we have harmony. But when one of the other is knocked off balance, the whole system can become disrupted. Microbes influence the production of hormones, such as insulin, and even neurochemicals, such as serotonin, so a disruption in the microbiome can have major consequences for our health. This balanced equilibrium is an ideal state, wherein the microbiome is safe and warm, and in turn digesting our food, producing amino acids, vitamins and minerals, and other chemicals that do many different things, including stimulating our muscles and bones. But many of our lifestyle decisions, especially when it comes to diet and exercise, can favor the growth of certain microbes over others. And many of our ‘bad’ decisions can favor the growth of microbes that can cause inflammation, and stop the production of important chemicals that support our health.
One perfect example of this is in weight gain. The microbiome influences weight gain, in part by changing the degree to which your body accesses energy from the food you eat. But your microbiome also changes circadian rhythms throughout your body, especially your liver, which leads to shifts in how your body stores energy. A diet heavy in fats and sugars leads to favor the growth of bacteria that cause gut inflammation and stop the production of chemicals called short-chain fatty acids, which also regulate insulin levels in your blood stream. These changes can also lead to an increase in bacteria that produce hydrogen sulfide (rotten egg smell), which enters the bloodstream and from there can disrupt how circadian clock genes work in your liver. This means that your liver perceives time differently to how your brain perceives time (which is mainly driven by light and dark). This de-coupling causes your body’s normal balance or homeostasis to be thrown into disarray, and one of the results is increased fat storage.
However, the animals we study in the lab can get fat for a lot of different reasons. They can have genetic defects that make them tubby. Or they can be fed a bad diet. Amazingly, in both these cases, the microbiome changes in ways that lead to increased inflammation, glucose intolerance, and ultimately even diabetes. And what’s even more amazing is that you can take that microbiome and transplant it into another mouse that’s raised germ-free, with no microbes of its own and that mouse will then become fat even if it doesn’t have the genetic defect or the bad diet. This shows that microbes can transmit obesity.
Interestingly, a diet high in fat and sugar can change your microbiome in ways that make it more likely that you will crave such foods, as well as craving more food overall. We don’t really understand the specific mechanism behind this yet, but interactions between the immune system, the microbiome and the brain, and the balance of neurotransmitters produced by bacteria in the gut, seem to disrupt normal hunger levels, causing a reduction in satiety and an increase in cravings.
So how do we treat this problem. If you have already made bad dietary choices, and changed your microbiome to one that promote obesity, what can you do to reverse this problem. Well, like any environment, it is necessary to change the selective pressure that allows certain organisms to flourish and others to decline. A recent study demonstrated that mice who have a obese promoting microbiome need to stay on a low fat/low carb diet for the equivalent of 9 human months to change the microbiome enough so that it stops promoting obesity when you eat the wrong food occasionally. This suggests that the obesity-promoting microbiome is very stable, and hard to shift into a non-obese promoting microbiome.
However, there are ways to accelerate this process. For example, probiotic therapy to reverse weight gain has gained some traction recently, at least in animal models. Mice fed a high fat diet lost weight after getting a mixture of three probiotics (Lactobacillus paracasei CNCM I-4270, L. rhamnosus I-3690 and Bifidobacterium animalis subsp. lactis I-2494). Their insulin function also improved. We don’t yet know if this regime will work for overweight people, but research is underway.
Recently one of my colleagues, studied weight gain and loss in children with Prader–Willi syndrome. These kids cannot stop eating, to the point where they will hurt people if those individuals fail to give up their food. It had been considered a genetic condition, but this study provided evidence that microbes are involved. Seventeen children with Prader-Willi syndrome were kept in the hospital and only allowed to eat a diet rich in non-digestible carbohydrates - essential a high fiber diet. This caused them to lose weight and changed their microbiomes dramatically. For example, they produced more acetate, a molecule used by other bacteria to make compounds that reduce inflammation by calming the immune system. Interestingly, there is evidence from this study that the children also exhibited an increased ability to control their appetite; although further study is needed to confirm this finding.
What is known is that you can tell whether someone’s lean or obese with up to ninety percent accuracy simply by looking at their microbiome. Although generally, it is reasonably easy to tell from just looking in a mirror. However, more studies are coming out all the time that suggest whether you respond to dieting by losing weight can also be predicted from the microbiome in your poop. Does this mean that a microbiome-based test for predicting diet success may be on the cards? Well surprisingly yes, a recent study demonstrated that the microbiome can be used to predict your glycemic response to different food stuffs. That means that by looking at your microbiome it is possible to determine your blood sugar level after eating certain types of food. We all have different responses to the same food. A company has now been formed on the basis of this research that uses stool microbiome analysis to predict the perfect diet for you. Day Two offers customers the opportunity to have a diet that will help naturally balance their blood sugar, reducing blood sugar spikes that can influence mood and even presage diabetes onset.
This is an exciting new field, and we all look forward to the day when we can pop a magic pill that helps regulate our weight without having to work hard at it. Until then, it is best to try and eat healthy, reduce your complex carbs, eat lots of leafy greens and colored vegetables (which feed your good microbes), and practice portion control. The microbiome offers many wonderful explanations for why we suffer from certain conditions, but it cannot absolve us of all responsibility for maintaining our own wellness.
This blog post was developed and augmented based on entries in my recent book, which provides evidence based advice on how microbes can influence your health and that of your children during pregnancy and the first 3 years of life.
(Hartstra et al. 2015; Zhang et al. 2015; P. J. Turnbaugh et al. 2009; Zeevi et al. 2015; Peter J. Turnbaugh 2017; Peter J. Turnbaugh et al. 2006, 2008; Leone et al. 2015; Gilbert et al. 2016; Wang et al. 2015)
Gilbert, Jack A., Robert A. Quinn, Justine Debelius, Zhenjiang Z. Xu, James Morton, Neha Garg, Janet K. Jansson, Pieter C. Dorrestein, and Rob Knight. 2016. “Microbiome-Wide Association Studies Link Dynamic Microbial Consortia to Disease.” Nature 535 (7610): 94–103. doi:10.1038/nature18850.
Hartstra, Annick V., Kristien E. C. Bouter, Fredrik Bäckhed, and Max Nieuwdorp. 2015. “Insights into the Role of the Microbiome in Obesity and Type 2 Diabetes.” Diabetes Care 38 (1): 159–65. doi:10.2337/dc14-0769.
Leone, Vanessa, Sean M. Gibbons, Kristina Martinez, Alan L. Hutchison, Edmond Y. Huang, Candace M. Cham, Joseph F. Pierre, et al. 2015. “Effects of Diurnal Variation of Gut Microbes and High-Fat Feeding on Host Circadian Clock Function and Metabolism.” Cell Host & Microbe 17 (5): 681–89. doi:10.1016/j.chom.2015.03.006.
Turnbaugh, P. J., V. K. Ridaura, J. J. Faith, F. E. Rey, R. Knight, and J. I. Gordon. 2009. “The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice.” Science Translational Medicine 1 (6): 6ra14-6ra14. doi:10.1126/scitranslmed.3000322.
Turnbaugh, Peter J. 2017. “Microbes and Diet-Induced Obesity: Fast, Cheap, and Out of Control.” Cell Host & Microbe 21 (3): 278–81. doi:10.1016/j.chom.2017.02.021.
Turnbaugh, Peter J., Fredrik Bäckhed, Lucinda Fulton, and Jeffrey I. Gordon. 2008. “Diet-Induced Obesity Is Linked to Marked but Reversible Alterations in the Mouse Distal Gut Microbiome.” Cell Host & Microbe 3 (4): 213–23. doi:10.1016/j.chom.2008.02.015.
Turnbaugh, Peter J., Ruth E. Ley, Michael A. Mahowald, Vincent Magrini, Elaine R. Mardis, and Jeffrey I. Gordon. 2006. “An Obesity-Associated Gut Microbiome with Increased Capacity for Energy Harvest.” Nature 444 (7122): 1027–31. doi:10.1038/nature05414.
Wang, Jingjing, Huang Tang, Chenhong Zhang, Yufeng Zhao, Muriel Derrien, Emilie Rocher, Johan E. T. van-Hylckama Vlieg, et al. 2015. “Modulation of Gut Microbiota during Probiotic-Mediated Attenuation of Metabolic Syndrome in High Fat Diet-Fed Mice.” The ISME Journal 9 (1): 1–15. doi:10.1038/ismej.2014.99.
Zeevi, David, Tal Korem, Niv Zmora, David Israeli, Daphna Rothschild, Adina Weinberger, Orly Ben-Yacov, et al. 2015. “Personalized Nutrition by Prediction of Glycemic Responses.” Cell 163 (5): 1079–94. doi:10.1016/j.cell.2015.11.001.
Zhang, Chenhong, Aihua Yin, Hongde Li, Ruirui Wang, Guojun Wu, Jian Shen, Menghui Zhang, et al. 2015. “Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.” EBioMedicine 2 (8): 968–84. doi:10.1016/j.ebiom.2015.07.007.