Obesogenic Gut Bugs: How Bacteria Can Make Us Fat

The microbiome and the brain are the chief regulators of adiposity and eating behavior in humans. In many respects, the microbiome is even more important than the brain. Obviously, it’s the processes of the brain that ultimately shape our thoughts and behavior. What’s important to recognize though, is that these processes, in turn, are greatly influenced by signals derived from other parts of the body, in particular the gastrointestinal microbiota and adipose tissue.

Some may perhaps go as far as to say that the brain is a puppet that’s under control of the microbes that colonize the body. This is obviously stretching the truth a bit; however, it does make an important point, which is that the brain is not an isolated organ; it’s greatly affected by what goes on in the rest of the body.

This is unfortunately something that has historically received little attention within conventional medical circles, including the parts of the medical community that are concerned with disorders of the mind. Over the past decade, as the research on the gut-brain axis has taken off, this has gradually started to change; however, a worryingly high number of people appear to still hold the belief that the brain is a lone wolf.

In this article, we’re not going to take an in-depth look at the science on the gut-brain axis. What I thought we’d do instead is to briefly talk about a single study that was published a few years back (1). This study has lingered in the back of my mind since I first discovered it a while back, in large part because I find it to be very interesting.

Microbes are more powerful than most people think

The experiment that the authors of the study – Na Fei og Liping Zao – conducted is a fairly simple one. During clinical research, they discovered, via gut microbiome testing, that a morbidly obese and diabetic man weighing 174.8 kg harbored a dysbiotic microbiota, rich in Enterobacter, a microbial genus heavy on opportunistic, endotoxin-producing pathogens. At the start of the experiment, Enterobacter made up 35% (!) of the man’s gut bacterial population.

When the obese and diabetic man was put on a whole foods diet rich in whole grains, traditional Chinese medical foods, and prebiotics, his body started to change. Various metabolic and inflammatory variables were gradually brought down to normal levels and the man lost 30.1 kg in 9 weeks and 51.4 kg in 23 weeks. That’s a lot of weight! Moreover, arguably even more interesting, at 9 weeks, the Enterobacter population of the study participant’s gut had markedly shrunk. It now only made up 1.8% of total gut bacteria. Moving forward, it kept shrinking. At 23 weeks, it was not detectable at all.

Can we conclude from this that the weight loss and health improvements were brought about by the gradual disappearance of Enterobacter from the participant’s gut? No… We can’t. Correlation doesn’t equal causation. Many factors are at play here. The experiment doesn’t clearly reveal how they are linked and what came first: the metabolic improvements and weight loss, or the loss of Enterobacter from the gut. Not only that, but we can’t exclude the possibility that there is no causal link between these things.

With all of that being said, it’s well-established that the bugs that reside in our guts greatly affect our immunity, circulating endotoxin levels, metabolism, and appetite, among other things (2, 3, 4, 5, 6). Hence, it seems highly plausible that part of the reason why the body of the obese participant in the above study changed so much following the dietary intervention is that the intervention altered the man’s gut microbiota. In other words, it seems likely that the microbiota mediated some of the favorable health effects produced by the dietary intervention.

In order to make some headway towards figuring out whether this had indeed been the case, the researchers isolated a bacterial strain from the Enterobacter population found in the study participant’s gut. The strain, which was shown to be of the species Enterobacter cloacae, was then transferred into the guts of germ-free mice.

Over the course of 1 week, the Enterobacter cloacae strain isolated from the obese human was transferred into the guts of two groups of mice, one eating a High-Fat Diet (HFD) and the other eating a Normal Chow Diet (NCD). Following this inoculation period, the mice in the HFD group started gaining a lot of weight. This weight gain was associated with various unfavorable metabolic shifts. Among other things, the infected mice eating a HFD expressed an insulin and leptin resistant phenotype. The mice eating a NCD, on the other hand, remained lean throughout the experiment.

What’s particularly interesting about the study is that the researchers also tested whether another bacterium, namely a strain of Bifidobacterium animalis, would induce the same obese phenotype as the Enterobacter cloacae strain in mice eating a HFD. It didn’t. Mice that were inoculated with Bifidobacterium animalis gained significantly less weight than mice inoculated with Enterobacter cloacae. This clearly suggests that obesity can’t be produced by just any bacterium.

Conventional mice fed a HFD tend to become obese. Germ-free mice, on the other hand, have been shown to be resistant to HFD-induced obesity. This clearly suggests that microbes are involved in processes related to body fat regulation in mice. The above experiment verifies that this is the case. Not only that, but it highlights the fact that some types of bacteria are a lot more problematic than others in the context of obesity and body fat regulation.

Reflections

Before we wrap up, I think it’s important to point out that the human gut microbiota is an extremely complex ecosystem composed of a wide variety of different microbes. In other words, no human gut is just composed of Bifidobacterium animalis, Enterobacter cloacae, or some other type of bacterium. Not only that, but humans differ from mice in several important respects and don’t eat a standardized HFD intended for experimental research purposes.

With that said, I think we can learn a lot from the study by Fei et al. Moreover, it’s important to point out that many other studies beside the one by Fei et al. suggest that microbes play a critical role in human body fat regulation (4, 5, 6, 7, 8, 9). There’s little doubt in my mind that one of the primary reasons why we’re today in the midst of an obesity epidemic is that a lot of people harbor a gut microbiota rich in proinflammatory bugs.

Practical applications

Diet composition is a major determinant of gut microbiota composition. This is clearly highlighted by the study by Fei et al. If you eat a diet that differs markedly from the type of diet that we humans evolved to eat, you will produce a gut microbiota that differs markedly from the type of microbiota that the human body evolved alongside. This, in turn, will make you fat and metabolically deranged, in part because certain gut microbes will make you chronically inflamed and influence your brain in such a way that you become inclined to eat more of the food that the microbes in question need to thrive.

A lot of overweight and obese people can undoubtedly “fix” their microbiota simply by changing their diet. Not everyone though. A person who harbors a severely dysbiotic microbiota may find that he has to incorporate additional microbiome restoration strategies into his health regimen in order to make some significant headway towards fixing his gut and bringing down the levels of inflammatory mediators circulating in his blood. He may for example find that he has to bring new bugs into his gut by eating fermented vegetables, performing one or more fecal microbiota transplantations, and/or exposing himself to friendly bacteria associated with healthy, lean people and pets.