New Finding Adds To Growing Evidence That Intestinal Bacteria Is Directly Linked To Disease
There's no doubt about it, bacteria keep us alive. They're thought to encode more than 3 million genes in the body, and this complexity of bugs may also be responsible for immune dysfunction that begins with a "failure to communicate" in the human gut, scientists say. Researchers have linked a species of intestinal bacteria to the onset of rheumatoid arthritis, the first demonstration in humans that the chronic inflammatory joint disease may be mediated in part by specific intestinal bacteria.
Health care of the future may include personalized diagnosis of an individual's "microbiome" to determine what prebiotics or probiotics are needed to provide balance.
A role for gut microbes in gastrointestinal function has been well documented since researchers first described differences in the fecal bacteria of people with inflammatory bowel disease.
The new findings by laboratory scientists and clinical researchers in rheumatology at NYU School of Medicine add to the growing evidence that the trillions of microbes in our body play an important role in regulating our health.
Using sophisticated DNA analysis to compare gut bacteria from fecal samples of patients with rheumatoid arthritis and healthy individuals, the researchers found that P. copri was more abundant in patients newly diagnosed with rheumatoid arthritis than in healthy individuals or patients with chronic, treated rheumatoid arthritis. Moreover, the overgrowth of P. copri was associated with fewer beneficial gut bacteria belonging to the genera Bacteroides.
"Studies in rodent models have clearly shown that the intestinal microbiota contribute significantly to the causation of systemic autoimmune diseases," says Dan R. Littman, MD, PhD, the Helen L. and Martin S. Kimmel Professor of Pathology and Microbiology and a Howard Hughes Medical Institute investigator.
"Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association," says Dr. Littman, whose basic science laboratory at NYU School of Medicine's Skirball Institute of Biomolecular Medicine collaborated with clinical investigators led by Steven Abramson, MD, senior vice president and vice dean for education, faculty, and academic affairs; the Frederick H. King Professor of Internal Medicine; chair of the Department of Medicine; and professor of medicine and pathology at NYU School of Medicine.
"At this stage, however, we cannot conclude that there is a causal link between the abundance of P. copri and the onset of rheumatoid arthritis," Dr. Littman says. "We are developing new tools that will hopefully allow us to ask if this is indeed the case."
The new findings, reported today in the open-access journal eLife, were inspired by previous research in Dr. Littman's laboratory, collaborating with Harvard Medical School investigators, using mice genetically predisposed to rheumatoid arthritis, which resist the disease if kept in sterile environments, but show signs of joint inflammation when exposed to otherwise benign gut bacteria known as segmented filamentous bacteria.
Rheumatoid arthritis, an autoimmune disease that attacks joint tissue and causes painful, often debilitating stiffness and swelling, affects 1.3 million Americans. It strikes twice as many women as men and its cause remains unknown although genetic and environmental factors are thought to play a role.
The human gut is home to hundreds of species of beneficial bacteria, including P. copri, which ferment undigested carbohydrates to fuel the body and keep harmful bacteria in check. The immune system, primed to attack foreign microbes, possesses the extraordinary ability to distinguish benign or beneficial bacteria from pathogenic bacteria. This ability may be compromised, however, when the gut's microbial ecosystem is thrown off balance.
"Expansion of P. copri in the intestinal microbiota exacerbates colonic inflammation in mouse models and may offer insight into the systemic autoimmune response seen in rheumatoid arthritis," says Randy S. Longman, MD, PhD, a post-doctoral fellow in Dr. Littman's laboratory and a gastroenterologist at Weill-Cornell, and an author on the new study. Exactly how this expansion relates to disease remains unclear even in animal models, he says.
Why P. copri growth seems to take off in newly diagnosed patients with rheumatoid arthritis is also unclear, the researchers say. Both environmental influences, such as diet and genetic factors can shift bacterial populations within the gut, which may set off a systemic autoimmune attack. Adding to the mystery, P. copri extracted from stool samples of newly diagnosed patients appears genetically distinct from P. copri found in healthy individuals, the researchers found.
To determine if particular bacterial species correlate with rheumatoid arthritis, the researchers sequenced the so-called 16S gene on 44 fecal DNA samples from newly diagnosed patients with rheumatoid arthritis prior to immune-suppressive treatment; 26 samples from patients with chronic, treated rheumatoid arthritis; 16 samples from patients with psoriatic arthritis (characterized by red, flaky skin in conjunction with joint inflammation); and 28 samples from healthy individuals.
Seventy-five percent of stool samples from patients newly diagnosed with rheumatoid arthritis carried P. copricompared to 21.4% of samples from healthy individuals; 11.5% from chronic, treated patients; and 37.5% from patients with psoriatic arthritis.
Rheumatoid arthritis is treated with an assortment of medications, including antibiotics, anti-inflammatory drugs like steroids, and immunosuppressive therapies that tame immune reactions. Little is understood about how these medications affect gut bacteria. This latest research offers an important clue, showing that treated patients with chronic rheumatoid arthritis carry smaller populations of P. copri. "It could be that certain treatments help stabilize the balance of bacteria in the gut," says Jose U. Scher, MD, director of the Microbiome Center for Rheumatology and Autoimmunity at NYU Langone Medical Center's Hospital for Joint Diseases, and an author on the new study. "Or it could be that certain gut bacteria favor inflammation."
The researchers plan to validate their results in regions beyond New York, since gut flora can vary across geographical regions, and investigate whether the gut flora can be used as a biological marker to guide treatment. "We want to know if people with certain populations of gut bacteria respond better to certain treatment than others," says Dr. Scher. Finally, they hope to study people before they develop rheumatoid arthritis to see whether overgrowth of P. copri is a cause or result of autoimmune attacks.
In addition to researchers from the NYU School of Medicine, investigators from Memorial Sloan Kettering Cancer Center and from the Harvard School of Public Health contributed to the study. Funding for this research comes from the National Institutes of Health, the Howard Hughes Medical Institute, and the American Gastroenterological Association.
6 SURPRISING FACTS ABOUT MICROBES IN YOUR GUT
1. What's in Your Gut May Affect the Size of Your Gut
Need to lose weight? Why not try a gut bacteria transplant?
New research published in the journal Science suggests that the microbes in your gut may play a role in obesity.
2. Probiotics May Treat Anxiety and Depression
Scientists have been exploring the connection between gut bacteria and chemicals in the brain for years. New research adds more weight to the theory that researchers call "the microbiome--gut--brain axis."
Research published in Proceedings of the National Academy of Science shows that mice fed the bacterium Lactobacillus rhamnosus showed fewer symptoms of anxiety and depression. Researchers theorize that this is because L. rhamnosus acts on the central gamma-aminobutyric acid (GABA) system, which helps regulate emotional behavior.
L. rhamnosus, which is available as a commercial probiotic supplement, has also been linked to the prevention of diarrhea, atopic dermatitis, and respiratory tract infections.
3. The More Bacteria the Better
While bacteria on the outside of your body can cause serious infections, the bacteria inside your body can protect against it. Studies have shown that animals without gut bacteria are more susceptible to serious infections.
Bacteria found naturally inside your gut have a protective barrier effect against other living organisms that enter your body. They help the body prevent harmful bacteria from rapidly growing in your stomach, which could spell disaster for your bowels.
To do this, they develop a give-and-take relationship with your body.
"The host actively provides a nutrient that the bacterium needs, and the bacterium actively indicates how much it needs to the host," according to research published in The Lancet.
4. Gut Bacteria Pass from Mother to Child in Breast Milk
It's common knowledge that a mother's milk can help beef up a baby's immune system. New research indicates that the protective effects of gut bacteria can be transferred from mother to baby during breastfeeding.
Work published in Environmental Microbiology shows that important gut bacteria travels from mother to child through breast milk to colonize a child's own gut, helping his or her immune system to mature.
5. Lack of Gut Diversity Is Linked to Allergies
Too few bacteria in the gut can throw the immune system off balance and make it go haywire with hay fever.
Researchers in Copenhagen reviewed the medical records and stool samples of 411 infants. They found that those who didn't have diverse colonies of gut bacteria were more likely to develop allergies.
But before you throw your gut bacteria a proliferation party, know that they aren't always beneficial.
6. Gut Bacteria Can Hurt Your Liver
Your liver gets 70 percent of its blood flow from your intestines, so it's natural they would share more than just oxygenated blood.
Italian researchers found that between 20 and 75 percent of patients with chronic fatty liver disease--the kind not associated with alcoholism--also had an overgrowth of gut bacteria. Some believe that the transfer of gut bacteria to the liver could be responsible for chronic liver disease.
How Do Probiotics Work
Probiotics work in many different ways by their production of antimicrobial substances (organic acids, hydrogen peroxide, and bacteriocins) that inhibit pathogen adhesion and degrade toxins produced by microbial invaders. Probiotics resist colonization by competing for binding sites as well as for nutrients with pathogens. In other words, they crowd out pathogens like candida and harmful E. Coli.
Probiotics secrete various proteins that stimulate the immune system both locally and throughout the body, boost intestinal brush border enzyme activity and increase secretory-IgA (a family of antibodies lining mucous membranes). Enzymes like lactase, sucrase, maltase, alpha-glucosidase, and alkaline phosphatase are enhanced by probiotics. Cholesterol and triglyceride blood levels are metabolized and lowered by healthy probiotic populations. Probiotics are able to resist translocation, defined as the passage of pathogens from the GI tract to extraintestinal sites such as the mesenteric lymph node (MLN), spleen, liver, kidneys, and blood.
Benefits of Probiotics
The following are the most well documented benefits of taking probiotics regularly:
- Weaken antibiotic resistant bacterial strains, attack new types of pathogens (supergerms) and infections in immuno-compromised people requiring treatment (i.e. resist opportunistic infections like candidiasis)
- Manufacture B vitamins (biotin, B3, B5, B6, folic acid, B12) and vitamin K
- Secrete lactase, an enzyme required to break down lactose in milk
- Act as anti-cancer factors (especially for bladder and bowel) by inhibiting bacteria that convert nitrates into nitrites
- Inhibit bacteria that secrete carcinogens
- Function as natural antibiotics against unfriendly bacteria, viruses and yeast like Candida albicans
- Enhance bowel function and elimination; prevent constipation
- Reverse diarrhea conditions (Crohn's disease, AIDS, Traveller's)
- Reduce or eliminate bloating, gas, straining and abdominal pain due to any cause
- Prevent skin problems, especially acne and other skin infections. (FYI - most chronic acne conditions in adults are often improved or eliminated by a good bowel flora balance).
- Protect against the adverse effects of radiation and pollutants
- Reduce blood levels of cholesterol and triglycerides
- Fight stress and food cravings and thereby prevent or reverse obesity
- Help eliminate bad breath
- Optimize sex hormone levels, enhance fertility and prevent osteoporosis
- Produce lactic acid, improve the digestibility of foods
- Oppose putrefactive bacteria like bacteroides associated with a meat-rich diet
- Treat eczema, psoriasis, ulcerative colitis, Crohn's Disease, irritable bowel syndrome, all cancers, gastritis, duodenitis, diverticulitis, food allergies, lactose intolerance, environmental allergies, urinary tract infections, vaginitis, other chronic infections (TB, AIDS, Herpes, venereal diseases) and autoimmune diseases (e.g. rheumatoid arthritis, polymyalgia rheumatica, ankylosing spondylitis, psoriasis, lupus, alopecia areata, scleroderma, thyroiditis, etc.)
Cultured dairy products like yogurt, acidophilus milk, buttermilk, sour cream, cottage cheese and kefir are the best known food sources of friendly bacteria. Equally effective probiotic food sources include cultured/fermented vegetables (cabbage, turnips, eggplant, cucumbers, onions, squash, and carrots). Other, lesser known or used food sources of probiotics are sauerkraut and sourdough breads. Ideally, one could get a good supply of probiotics from one or more of these diverse foodstuffs. If dietary sources are not easily available, supplemental probiotic powders and capsules are good alternatives. Choose a brand that has at least 3 different strains of friendly bacteria and between 6 -- 15 billion live organisms.
Karen Foster is a holistic nutritionist, avid blogger, with five kids and an active lifestyle that keeps her in pursuit of the healthiest path towards a life of balance.