A Step Forward in Figuring Out the Microbiome/Weight Gain Connection

Today, for your reading pleasure, a quick summary of a super interesting article I spotted in the journal, Nature Metabolism, over this past weekend.  As you know from my (many) past posts on the topic of obesity, it is  NOT a simple question of how much you eat = how much fat is on your body.  What you eat probably matters as much as how much you eat, and more than that, there are an incredible number of co-factors that complicate the question.  (After all, how many of us know people who eat like they have a bottomless pit inside instead of a stomach, yet remain skinny?)  Those co-factors involve everything from stress levels to genetics to activity levels to the composition of your microbiome.  As the authors of today’s paper succinctly state in the opening sentence of their paper, “Obesity and obesity-related metabolic disorders are linked to the intestinal microbiome.”[i]

This latter factor, in fact, has actually led scientists to believe that in a way, the tendency toward fatness is “catching.”  That is, since people living in the same households tend to share gut bugs, those that predispose a body toward storing fat can be passed around.  Interestingly, a summary article of this study that I found on the website, Science Alert, states, “Recent studies have even suggested that leanness or weight gain could be contagious, through the spread of different microbes.”[ii]

A little biology before I launch into my explanation of today’s paper.  Carnitine is derived from amino acids, and is found in animal products, as well as being produced by the human body.  It is used by our bodies to transport fat molecules into the mitochondria of cells.  Mitochondria are where energy for the cells of the body is produced. These scientists found, in mice exposed to microbes, a gut bacterial metabolite circulating in the blood called delta-valerobetain and oddly, they did not find it in germ-free mice. They then discovered that this metabolite led to decreased levels of carnitine, which, in turn meant that the mice were unable to make efficient use of fat in their diets for energy. Thus, mice fed high fat diets similar to “western diets,” stored that extra dietary fat as adipose tissue:  the mice gained weight, as well as accumulated fat in their livers.

They have not as yet completely proven this same effect in humas but the data look promising.  In a study of 214 humans, the blood levels of the bacterial metabolite delta-valerobetaine and carnitine – as well as body fat – match up. That is, the average blood level of delta-valerobetaine was 40% higher in people with a BMI over 30 (defining obesity) as those with lower BMIs.  The scientists hypothesize that certain kinds of gut bacteria produce more delta-valerobetaine than others, and levels of those bacteria are likely determined mainly by what is being eaten, but also, cofactors such as those mentioned above: who we live with, what medications we take, and so forth.

Delta-valerobetaine is also present in commonly eaten foods, by the way, including meat and milk, and actually has benefits as well:  it seems to reduce cancer cell viability.  The belief is that, from an evolutionary perspective, it makes sense that our gut bugs produce it, in order to protect us from starvation when food is scarce:  it makes us efficient at storing fat on our bodies.  Unfortunately, in societies like ours, where food is abundant, that efficiency has an adverse effect.

______________________________________

[i] Liu, K.H., Owens, J.A., Saeedi, B. et al. Microbial metabolite delta-valerobetaine is a diet-dependent obesogen. Nat Metab 3, 1694–1705 (2021). https://doi.org/10.1038/s42255-021-00502-8

[ii] https://www.sciencealert.com/scientists-discover-how-some-gut-microbiomes-could-be-promoting-obesity