A problem with an immune system gene may lead to obesity and type 2 diabetes, a study done in mice suggests.
Mice gained weight and developed health problems when they had a genetic defect that impairs some immune cells. The immune problems were linked to shifts in the gut microbiome. That’s the collection of friendly bacteria and other microbes living in the intestines. Altering the gut microbe mix could increase the amount of fat absorbed from food, researchers say. They reported their findings July 26 in Science.
More studies are needed to see if these findings hold up in humans. If so, it might be possible to boost a person’s immune system function. That might, in turn, help prevent obesity and related health problems.
People with obesity and those with type 2 diabetes also have an unusual gut microbe mix and immune system deficiencies. The people’s bacteria mixes are similar to those seen in the mice. And obese people’s immune systems don’t always work very well, says June Round. She’s a microbiome researcher who worked on the new study. She’s at the University of Utah School of Medicine. That’s in Salt Lake City. “It’s possible that things that are happening in our mice are also happening in individual [humans],” she says.
The researchers studied mice that had a defect in the Myd88 gene. That defects stops the mice from making the Myd88 protein in their T cells. T cells help the immune system recognize and kill bad bacteria and viruses.
The researchers noticed that the mutant mice started gaining weight at about 5 months old. By about a year old, those mice weighed up to 60 grams (about 2 ounces). That’s about twice as much as a normal mouse. The mutant mice also had a problem associated with obesity called insulin resistance. This is a condition in which the body’s cells can’t process dietary sugars efficiently. It is a hallmark of type 2 diabetes in people.
Round and her team found that the mice had reduced activity of some T cells called T helper cells. The job of these helper cells is to tell other immune cells, called B cells, to make microbe-fighting antibodies. But in these mice, the B cells made less of these antibodies.
The researchers found that obese mice had fewer types of gut microbes compared to normal mice. There were lower numbers of Clostridia bacteria in the small intestine. And there were increased numbers of Desulfovibrio bacteria. That pattern also has been seen in obese people and people with type 2 diabetes.
Some Clostridia bacteria in the mutant mice were coated with many antibodies. This suggests those bacteria were targeted for destruction. But other Clostridia species had few antibodies clinging to them. Sometimes antibodies help bacteria instead of killing them. Clostridia with few antibodies might not grow well in the gut.
Desulfovibrio also was more heavily antibody-coated than usual. But the researchers aren’t sure how that might affect the bacteria’s growth.
Giving heavy mice more Clostridia led to weight loss. But the researchers couldn’t make normal mice overweight just by giving them Desulfovibrio. That’s probably because the immune system in normal mice can keep the bacteria in check, Round says.
Altering the microbiome may affect how much fat is absorbed in the small intestine. Giving the mutant mice extra Clostridia reduced the production of a protein involved in fat absorption. But giving the mice Desulfovibrio had the opposite effect. It increased the protein’s production. This suggests that Clostridia protect against obesity. On the other hand, Desulfovibrio appear to promote obesity.
Scientists had known that both gut microbes and diet help to determine body weight. But the new study “shows that the immune system is really important in how that plays out,” says Lora Hooper. She’s a microbiologist and immunologist. She does research at the University of Texas Southwestern Medical Center. That’s in Dallas. She wasn’t involved in the study, but she co-wrote a commentary on the work in Science.
The work raises many questions, Hooper says. One of the biggest is why our microbiome is in charge of how much fat the gut absorbs. She doubts that Clostridia evolved to protect against obesity. That’s a modern-day problem. Instead, she thinks that maybe increased fat absorption evolved to deal with having too much of certain gut bacteria. The calories from the extra fat would give the body extra energy to fight the bacteria.
antibody Any of a large number of proteins that the body produces from B cells and releases into the blood supply as part of its immune response. The production of antibodies is triggered when the body encounters an antigen, some foreign material. Antibodies then lock onto antigens as a first step in disabling the germs or other foreign substances that were the source of those antigens.
bacteria (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals). Bacteria are one of the three domains of life on Earth.
B cell A type of small white blood cell (also known as a B lymphocyte), which plays an important role in the immune system. Made in the bone marrow, these cells mature into plasma cells, and serve as the source of antibodies.
calorie The amount of energy needed to raise the temperature of 1 gram of water by 1 degree Celsius. It is typically used as a measurement of the energy contained in some defined amount of food. The exception: when referring to the energy in food, the convention is to call a kilocalorie, or 1,000 of these calories, a "calorie." Here, a food calorie is the amount of energy needed to raise 1 kilogram of water 1 degree C.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
commentary (in science) An opinion piece, often written to accompany — and add perspective to — a paper by others, which describes new research findings.
diabetes A disease where the body either makes too little of the hormone insulin (known as type 1 disease) or ignores the presence of too much insulin when it is present (known as type 2 diabetes).
diet The foods and liquids ingested by an animal to provide the nutrition it needs to grow and maintain health. (verb) To adopt a specific food-intake plan for the purpose of controlling body weight.
fat A natural oily or greasy substance occurring in plants and in animal bodies, especially when deposited as a layer under the skin or around certain organs. Fat’s primary role is as an energy reserve. Fat also is a vital nutrient, though it can be harmful if consumed in excessive amounts.
function (in math) A relationship between two or more variables in which one variable (the dependent one) is exactly determined by the value of the other variables.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
gut An informal term for the gastrointestinal tract, especially the intestines.
immune (adj.) Having to do with the immunity. (v.) Able to ward off a particular infection. Alternatively, this term can be used to mean an organism shows no impacts from exposure to a particular poison or process. More generally, the term may signal that something cannot be hurt by a particular drug, disease or chemical.
immune system The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.
impair (n. impairment) To damage or weaken in some way.
insulin A hormone produced in the pancreas (an organ that is part of the digestive system) that helps the body use glucose as fuel.
insulin resistance A condition where the body begins to ignore the presence of insulin, a hormone needed to help move energy (sugar) from the blood and into cells where it can fuel their activities. Insulin resistance is an early symptom of people at risk of developing type 2 diabetes.
microbe Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.
microbiology The study of microorganisms, principally bacteria, fungi and viruses. Scientists who study microbes and the infections they can cause or ways that they can interact with their environment are known as microbiologists.
microbiome The scientific term for the entirety of the microorganisms — bacteria, viruses, fungi and more — that take up permanent residence within the body of a human or other animal.
mutation (v. mutate) Some change that occurs to a gene in an organism’s DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.
obesity (adj. obese) Extreme overweight. Obesity is associated with a wide range of health problems, including type 2 diabetes and high blood pressure.
overweight A medical condition where the body has accumulated too much body fat. People are not considered overweight if they weigh more than is normal for their age and height, but that extra weight comes from bone or muscle.
protein A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.
resistance (as in drug resistance) The reduction in the effectiveness of a drug to cure a disease, usually a microbial infection. (as in disease resistance) The ability of an organism to fight off disease.
salt A compound made by combining an acid with a base (in a reaction that also creates water). The ocean contains many different salts — collectively called “sea salt.” Common table salt is a made of sodium and chlorine.
species A group of similar organisms capable of producing offspring that can survive and reproduce.
T cells A family of white blood cells, also known as lymphocytes, that are primary actors in the immune system. They fight disease and can help the body deal with harmful substances.
type 2 diabetes (see also diabetes) A disease caused by the body’s inability to effectively use insulin, a hormone that helps the body process and use sugars. Unless diabetes is controlled, a person faces the risk of heart disease, coma or death.
Journal: C. Petersen et al. T cell–mediated regulation of the microbiota protects against obesity. Science. Vol. 365, July 26, 2019, p. 340. doi: 10.1126/science.aat9351.
Journal: Y. Wang and L.V. Hooper. Immune control of the microbiota prevents obesity. Science. Vol. 365, July 26, 2019, p. 316. doi: 10.1126/science.aay2057.