Can Helminths Help Alleviate the Obesity Epidemic? The Evidence (Slowly) Mounts

Remember last week when I told you all that I have a million great new pieces of research to write about?  Well, things have only gotten worse(or is it better?!) since then.  I found a bunch more stuff to keep us all very busy these next few weeks.

Which is good news, I guess!

Today I am turning back to the topic of helminths because I found a pretty incredible article on a topic that is of particular interest to me.  As a nutritionist, one of my biggest concerns is the growing epidemic of obesity plaguing the industrialized world, as my regular readers know. A quick look at the latest statistics:  according to the CDC, 39.8% of adults in the USA are obese (during 2015-2016)[i].  A 2017 article in Forbes points out that, “…nearly 4 in 10 U.S. adults have a body mass index classifying them as obese. Adult obesity rates have continued to increase steadily since the turn of the century, rising from 30.5 percent in 1999-2000 to 39.6 percent in 2015-2016, a record high. Young Americans have also been piling on the pounds and the obesity rate among the country’s youth (aged 2-19 years old) currently stands at 18.5 percent.”  But that’s only a part of an increasingly-grim picture as, “…just over 70 percent of all Americans are either overweight or obese, meaning people with normal weight levels are now a minority.”

70%!  Holy cow.

Over the years since starting this blog, I have looked at various pieces of research wherein scientists are trying to figure out the cause of this explosion of obesity.  There is no simple answer:  it’s most certainly not just “people are eating too much.”  Yes, diet is a major piece (probably THE major piece – remember my post of a few weeks ago about increased consumption of fructose? ), but there are many other factors to take into consideration.  For example, biome depletion also plays a major role.

In fact, back in April 2018, I wrote about research into bacterial microbiome alterations and obesity.  In that experiment, scientists from the University of Chicago “…started with germ-free mice and found that even when fed high fat foods, they did not gain weight as the fats were excreted with their stool.  However, mice who have a very high level of non-pathogenic gut bacteria, did gain weight.  Very rapidly, the microbes in their small intestines changed, with increasing amounts of Clostridiaceae and Peptostreptococcaceae, the former of which in particular appears to be responsible for fat absorption.  Levels of Bifidobacteriacaea and Bacteriodacaea, microbial families associated with leanness, rapidly decreased.”

So obviously diet is a key factor,  and also, research into microbiome alterations associated with obesity continues to grow.  But again, that is only one “ome” native to the human ecosystem. In March of 2018, I also wrote about research on the relationship of obesity to macrobiome depletion.  Those researchers found that colonizing mice with the helminth, Heligmosomoides polygyrus (Hp), resulted in “…significantly attenuated obesity.”  They noted that the colonized mice also had highly improved blood markers, like reduced glucose and triglyceride levels and higher levels of regulatory cytokines (which reduce inflammation), and they concluded, “The significant inhibitory effect of H. polygyrus infection on diet-induced obesity in our model supports the idea that helminth parasites, which infect millions of people worldwide, particularly in the developing world, may have beneficial metabolic effects. Our results also support the potential for helminths as a new class of biologics in treating inflammatory diseases and metabolic disorders….[R]esults from our study raise the intriguing possibility of using helminths as novel, safer and effective therapeutics in the treatment of obesity and other immune and metabolic disorders.”

So now, back to the pearl I discovered this past week.

Japanese researchers, expanding upon this helminth research, looked in detail at the mechanism by which helminths protect against obesity.[ii] As they point out, “Several lines of evidence indicate an inverse correlation between helminthic infections and obesity as well as inflammation-mediated disorders, suggesting that helminths may have suppressive effects on these diseases.”  They go on to say though that the “…protective mechanism involved in how helminths suppress obesity are largely unknown.”  So – they wanted to figure out how it all works.

There are several metabolic control systems in the body that are meant to protect us from obesity, including one that tells fat cells (adipocytes) to burn calories and convert them to heat, as opposed to storing them as more fat.  There is a protein expressed in the mitochondria (the powerhouse of every cell in your body) of adipocytes called uncoupling protein 1 (UCP1).  UCP1 tells the cell to convert fat and glucose (fuel) to heat as opposed to storing it as more fat.  UCP1 is activated by the hormone norepinephrine (NE), which is a major chemical messenger in your body.  NE is released from nerves, including those that are distributed through your body fat.  So to summarize this:  norepinephrine stimulates the production of UCP1, which, in turn, tells the fat cell to burn and not store fat.

Back then to our Japanese scientists…

They fed mice high fat diets which rapidly cause major weight gain.  Again though, as in the previous study, those mice who were given helminths first (also Hp) were protected from gaining weight.  In fact, the obese mice who were given helminths and who were still continually fed a high fat diet actually lost weight and had improved dyslipidemia (elevated bad cholesterol/low good cholesterol).  These findings completely replicated those of the 2018 study.

As these scientists knew that the presence of helminths beneficially improves the bacteria of the gut (increasing beneficial, anti-inflammatory species and decreasing pathogenic, pro-inflammatory ones), they hypothesized that this protective effect was due to this modulation of the bacterial microbiome. And guess what?  “We found that helminthic infection affected gut bacteria, resulting in increased NE production that upregulated UCP1 in adipose tissues.”  Wow, right?!

To double check that they had correctly pinpointed the mechanism of action, they first gave some mice an agent to essentially block norepinephrine in the adipocytes.  Sure enough, even mice with the helminths on board gained weight:  “Thus, the protective role of Hp infection against obesity is dependent on NE, presumably by inducing UCP1 for energy expenditure in adipocytes.”  They then wanted to make sure that the source of the increased norepinephrine was the gut bacteria and not the mice’ own nervous systems. They noted that giving a chemical to block NE production led to a “completely suppressed NE production in adipose tissue” BUT mice who had helminths “still contained substantial amounts of NE after treatment…suggesting the existence of other sources of NE besides sympathetic nerves.” They treated a group of mice with antibiotics to reduce the intestinal bacteria and found that doing so, “…decreased both the NE concentration and expression of UCP1 in Hp-infected obese mice, resulting in the attenuated suppression of weight gain.”  So yup, the source of the protective norepinephrine in the helminth-colonized mice was the gut bacteria.

Much to my delight, they did then zero in on which bacteria were producing the NE.  Mice that were given helminths had more Firmicutes and Proteobacteria compared to the mice without helminths and “…previous studies reported that two bacteria genera, Bacillus and Escherichia belonging to Firmicutes and Proteobacteria, respectively, produced NE in the intestines.”  Levels of both were greatly increased in the mice with helminths and “…NE concentration in Hp-infected obese mice was closely correlated with the amount of those bacteria.”  That is, the more Bacillus and Escherichia in the intestine, the higher the levels of norepinephrine.

Obviously, these findings have yet to be replicated in humans.  We can only hope, as always, that such studies happen soon as we, in the industrialized world, only continue to get fatter and rates of obesity-associated illnesses continue to climb.

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[i] https://www.cdc.gov/obesity/data/adult.html

[ii] Shimokawa, C, Obi, S, Shibata, M, Olia, A, Imai, T, Suzue, K, Hisaeda, H.  Suppression of obesity by an intestinal helminth through interactinos with intestinal microbiota.  American Society for Microbiology: Infection and Immunity. 2019. Apr 2019, IAI.00042-19; DOI: 10.1128/IAI.00042-19