The Link Between Body Weight & The Immune System

If life was that simple, diets would actually work, middle aged people would not suddenly start to gain weight despite eating and moving similarly year after year, and no one would have to endure feeling guilty when with that one friend with the really active metabolism that can eat anything who says “I can’t gain weight even if I try.”

It appears as if some people have a gut that is more efficient than others when it comes to extracting calories from food; two people can eat the exact same piece of pizza and their bodies will absorb different amounts of energy, and this calorie converting ability can change over time and with other variables. 

Trillions of microbes in the intestine and how they work with each other and another variable that is just beginning to gain attention may be the solution, and that other variable is the immune system which determines the levels of inflammation in the gut that shapes the way food is digested, how many calories are absorbed, and how many nutrients pass through. 

This relationship between weight gain and microbes has been largely overlooked, but similar effects have been known in animals for decades. Just recently antibiotics have been shown to kill off microbes that normally occur in the gut to help digest food, breaking down nutrients helps them to pass through the walls of the bowel, meaning these microbes serve as a gatekeeper for what actually makes it into the body. 

Killing of these microbiomes carries consequences as a decrease in diversity is associated with obesity. The use of antibiotics exploded in the 20th century, so this should come as no surprise that this rise coincides with the obesity epidemic. To some this may be seen as a contrived correlation as many things have been increasing since the 1950s, but simply dismissing the relation would require ignoring the growing body of evidence of metabolic health being inseparable from the health of gut microbes.

Microbiomes of obese mice have fewer Bacteroides and more Firmicutes speices of bacteria in their guts than their lean counterparts; biochemical analyses shows this ratio makes the microbes better at harvesting energy. Even when the mice ate the same type and amount of food the bacterial populations meant some developed metabolic problems while others did not; and these bacterial patterns have been confirmed in obese humans. 

The microbiome associated with obesity has also been found to be transferable by Jeffery Gordon at Washington University in 2013. Gut bacteria was taken from pairs of human twins of which only 1 was obese then given to mice; mice given bacteria from the obese samples were found to quickly gain weight while the others did not. Gut bacteria transferred between humans via fecal transplants is an experimental sort of reset of the microbiome, research shows adding a single bacterial species to the gut can alter metabolism. A proof of concept study published in Nature Medicine showed those taking a probiotic containing Akkermansia muciniphila saw improvements including weight loss. 

Studies have shown that obese adults mount less effective immune responses to vaccines, and overweight as well as underweight indiviuals have elevated rates of infection which were thought to be effects of obesity and not the causes. Obesity and leanness appears to be transmissible through microbiome, “...metabolic disease turns out to be, in some ways, like an infectious disease,” says Lora Hooper of University of Texas Southwestern Medical Center. 

“When I started my lab there wasn’t much known about how the immune system perceives the gut microbes,” Hooper says. “A lot of people thought the gut immune system might be sort of blind to them.” “... it was obvious that this couldn’t be the case… human gut is host to about 100 trillion bacteria....serve vital metabolic functions, but can quickly kill a person if they get into the bloodstream…” “So clearly the immune system has got to be involved in maintaining them,” she says. Even subtle changes in the functioning of the immune system could influence microbial populations—and, hence, weight gain and metabolism.

University Of Utah researchers tested biomes of mice with and without immune alteration to study how immune changes may cause obesity; healthy mice were found to have an abundance of bacteria from the Clostridia genus and few from Desulfovibrio, and their guts let more fat pass through. Those with altered immune systems had fewer Clostridia and more Desulfovibrio which helped the gut absorb more fats from food, these mice gained more weight and exhibited signs of type 2 diabetes; it is not known whether this applies to humans, but reduced Clostridia and increased Desulfovibrio are seen in those with type 2 diabetes and obesity. 

These experiments demonstrated the principle of the immune system helping to control the composition of the gut microbiome, which is done by regularly mounting low level immune responses to keep bacteria populations in check. Meaning that inflammation isn’t always bad, the role of the immune system in the gut is to maintain balance, changes to these defenses over time or as a result of illness can cause certain species to flourish at the expense of others. 

“Although we know that, on the balance, diet is the strongest contributor to gut microbiome composition this study suggests that when immune control of the colon breaks down, growth can become unchecked and cause problems with metabolic regulation,” says Steve Lindemann of Purdue University. According to Lindemann the immune system regulates inhabitants of the small intestine as a checkpoint to weed out the bad and allow good to progress as rapidly as possible. 

If similar changes can translate to have comparable effects in humans, it may have far reaching implications for human diets. A person’s microbes and those contained in food would have to be taken into account as a component of the flimsy “calories in calories out” equation. Those trying to lose or maintain weight may think that trying to adjust their own microbiomes with probiotics may be the solution, but the answer is not that simple.

“A lot of the recent research on probiotics suggests it’s really not easy to keep and sustain new communities,” says Zac Stephens of the University of Utah. “It may well be that your immune response gets ‘stuck’ at an early age based on what you’ve exposed it to. Probiotics might not be enough to change a person’s microbiome, because your immune system determined early on that certain microbes are either appropriate or inappropriate in your gut.” “Keeping diverse gut microbes with diverse dietary sources is probably the safest advice for now,” he says. “That will stimulate a healthy, strong immune system that can learn and regulate and do all the things it does, in ways we’re just beginning to understand.”

This makes nutritional guidelines somewhat more inscrutable, and undermines the simplistic character judgements that are often associated with body weight. Viewing obesity as a manifestation of the interplay between many systems, genetics, microbes, and environments invites a new understanding of human physiology that has changed along with human relationships to the species in and around us. As science continues to make new discoveries they dispute the idea of weight as a simple character flaw and reveals it to be the self destructing myth it has always been.