Can Pro-Inflammatory Gut Bacteria Cause Obesity?

The microbiome and the brain are the chief regulators of adiposity and eating behavior in humans. In many respects, the microbiome is even more influential than the brain. While the many processes occurring in the brain ultimately shape our thoughts and behavior, they are in turn heavily influenced by signals issuing from other areas—like the gastrointestinal microbiome and adipose tissue.

Some experts even characterize the brain as a puppet controlled by the body’s microbial colonists. This is obviously a stretching the truth a bit. Still, it does reinforce the important point that the brain is not an isolated organ; it’s significantly affected by what goes on in the rest of the body.

This fact is unfortunately under-recognized within conventional medical circles, including among mental- and behavioral-health specialists. Over the past decade, as the research on the gut-brain axis has taken off, this has gradually started to change; however, an astonishingly large number of medical professionals still seem to perceive the brain as an independent actor.

My intention here is not to take an in-depth look at the science on the gut-brain axis. Instead, I want to address the implications of a single study published a few years back that has lingered in the back of my mind since I first discovered it. This study makes a potent statement about the influence wielded by our bacterial inhabitants.

Microbes: More Powerful Than Most People Think

The study to which I refer was fairly simple. During clinical research, the two authors discovered—via gut-microbiome testing—that a morbidly obese, diabetic man harbored significant dysbiosis: a bacterial community rich in Enterobacter, a microbial genus rife with opportunistic, endotoxin-producing pathogens. At the start of the experiment, Enterobacter comprised 35 percent of the man’s gut bacteria.

When the 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 gradually tapered down to normal levels, and the man lost 30.1 kg (66.22 lb) in 9 weeks—and 51.4 kg (113.08 lb) in 23 weeks. Even more interestingly, at 9 weeks, the Enterobacter population of the subject’s gut had shrunk markedly. It now made up only 1.8 percent of his total gut bacteria. Moving forward, it kept shrinking. At 23 weeks, it was completely undetectable.

Now, it would be irresponsible to conclude from this that the gradual disappearance of Enterobacter from the participant’s gut caused his weight loss and improved health markers. Correlation does not equal causation; many factors are at play here. It is unclear which occurred first: the metabolic improvements and weight loss, or the loss of Enterobacter from the gut. Perhaps there is no causal link at all.

Still, it’s well-established that our gut bugs greatly affect our immunity, circulating endotoxin levels, metabolism, and appetite, among other markers.Hence, it seems highly plausible that the dietary intervention exerted such strong health effects because it altered the man’s gut microbiota, which mediated some of the various effects.

In order to assess whether this had indeed been the case, the researchers isolated a bacterial strain, Enterobacter cloacae, from the Enterobacter population found in the study participant’s gut. They then transferred this strain into the guts of germ-free mice.

Over the course of a week, the Enterobacter cloacae strain was transferred into the guts of two groups of mice, one eating a high-fat diet (HFD) and the other eating a normal mouse-chow diet (NCD). Following this inoculation period, the mice in the HFD group started gaining a lot of weight, along with various other unfavorable metabolic shifts. Among other effects, the infected mice eating the HFD expressed an insulin- and leptin-resistant phenotype. The mice eating the NCD, on the other hand, remained lean throughout the experiment.  

The researchers also tested whether another bacterium, 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 seems to suggest that obesity can’t be produced by just any bacterium.

Normal 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 observation, and the aforementioned study, clearly suggest that microbes are involved in body-fat regulation processes in mice. They also highlight the fact that some types of bacteria are uniquely problematic in the context of obesity and body-fat regulation.

Reflections and Caveats

We must remember that the human gut microbiome is an extremely complex ecosystem, comprised of a wide variety of different microbes. In other words, no human gut is composed entirely of Bifidobacterium animalis, Enterobacter cloacae, or any other individual strain. Additionally, humans differ strikingly from mice in several important physiological aspects, and are not confined to standardized, high-fat diets designed for research.

Still, it seems we can learn a lot from the above study—which is only one among many indicating that microbes play a critical role in human body-fat regulation. I have little doubt that the current obesity epidemic is largely due to the fact that a lot of people harbor a gut terrain rich in proinflammatory bugs.

Diet is a major determinant of gut-microbial composition. This is clearly highlighted by the aforementioned study. If you eat a markedly different type of diet from that which we evolved to eat, you will promote a gut microbiome that differs markedly from that with which we evolved to corexist. This can encourage fat accumulation and metabolic derangement, in part because certain gut microbes will drive you to eat more of the food that they need to thrive (e.g., processed carbohydrates).

Many overweight and obese people may be able to “fix” their microbiomes simply by changing their diets; not everyone can, though. A person with severe gut dysbiosis may find that they have to incorporate additional microbiome-restoration strategies into their health regimen to reduce the levels of inflammatory mediators circulating in their blood. Eating fermented vegetables, undergoing fecal microbial transfer (FMT), and other interventions can be valuable in this regard. With time and care, they can cultivate a more weight-friendly gut terrain.

References:

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