The Microbiome and Gastrointestinal Disorders From Mayo Clinic
Although many of us think of the gastrointestinal tract as little more than a tube to move food and waste through the body, it is actually a very complex and sophisticated barrier system. The human gut, a world unto itself, teems with bacteria, viruses, and fungi. This population of microbes, called the gut microbiota, contains hundreds of different species, and each species carries its own complement of genes that are separate from the genes of their human host.1,2
Although this might sound disturbing, most of these resident microbes are beneficial, even necessary to good health. Scientists now know that human cells and genes alone do not account for the whole story of health and development.
The microbe populations that live in and on different parts of the body – referred to as the microbiome – play a critical role as well. For example, the gut microbiota break down undigested food to provide essential vitamins, such as vitamin K, biotin, and other B vitamins.
As with most things in health, balance is key. If certain microbes in the gut grow unchecked, then the microbiota becomes unbalanced. Likewise, if healthy microbe numbers fall, then disease can occur. Imbalances in the gut microbiota are linked to several adverse gastrointestinal (GI) conditions, including irritable bowel syndrome, Clostridioides difficile (C. difficile) infection, celiac disease, inflammatory bowel disease, and even some forms of cancer.1,3
The connection between the gut microbiota and GI health is a very active area of current research. If imbalances in the gut microbiota can cause diseases, then restoring balance might help cure them. Better yet, researchers say, perhaps monitoring and maintaining balance could prevent some adverse GI conditions from ever developing.
Together in health
Although a number of different types of microbes make up the gut microbiota, by far the majority are bacteria – at last count, more than 2,000 different species.4 Researchers believe a rich diversity of bacterial species contributes to better health. Studies have connected greater bacterial diversity in the gut to a lower risk of certain diseases.
A balanced gut microbiota creates a symbiotic relationship that benefits the host and the resident microbes. Food that can't be digested by the body, such as the fiber in complex carbohydrates, provides nutrition for particular types of bacteria. In return, the bacteria produce compounds that help maintain human health.
For instance, bacteria in the colon ferment undigested fiber to produce nutrients and short-chain fatty acids such as butyrate. Butyrate, the main fuel for colon cells, helps move indigestible food through the colon, enhances blood flow to the organs, and may prevent the development of colon cancer.5
In addition to providing nutrients, the gut bacteria and their byproducts influence human health by:
- Strengthening the lining of the gut (the epithelium) by modulating materials that pass through the cells of the gut’s wall, which protects the body from invasion by disease-causing (pathogenic) viruses and bacteria
- Helping the immune system regulate inflammation, a key defense mechanism that can cause disease if not properly controlled
- Aiding communication between digestive organs and the nervous system
Along with the healthy bacteria that populate the gut, there are harmful species, such as C. difficile. Although in a balanced gut microbiota the cooperative bacteria keep harmful bacteria in check, sometimes the populations may fall out of balance.
There are several factors that can impact the composition and function of our gut bacteria:5
- Stress (physical and psychological)
- Antibiotics and other drugs
- Environment, such as pets
- Body weight
The symbiotic microbes keep potentially harmful microbes out of the gut by competing for limited nutrients. The gut microbiota also supports the body’s response to invading microbes by facilitating the release of secretory immunoglobulin A (sIgA) antibodies in the mucous membranes in the GI tract. Certain bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, can break through that barrier, however, by releasing chemicals that destroy sIgA.
Antibiotics and intestinal health
Since their discovery, antibiotics have been used to treat ailments caused by bacteria, such as sinus infections, strep throat, tuberculosis, and cholera. Although antibiotics destroy pathogenic bacteria, these drugs also kill beneficial bacteria.
In fact, broad-spectrum antibiotics, such as amoxicillin, affect nearly one-third of the bacteria species in the gut and can cause rapid decreases in bacterial diversity.6 Although the microbiota can often handle the disruption and quickly return to balance, for some people the decreased population of beneficial bacteria provides an opportunity for harmful bacteria to flourish.5
Antibiotic use has been connected to infections such as C. difficile and Salmonella, as well as a host of other adverse conditions, such as inflammatory bowel disease (including Crohn’s disease), celiac disease, and obesity.5 For example, babies treated with antibiotics in the first year of life have an increased risk for developing inflammatory bowel disease. And the more the child is exposed to antibiotics, the higher the risk.1,2
This does not mean antibiotics shouldn’t be used – they can be lifesaving. However, they should be used only when prescribed properly and judiciously by a health-care professional.
The gut microbiota-disease connection
Many adverse GI conditions are linked to disruptions of the gut microbiota.5
1. Inflammatory bowel disease
Inflammatory bowel disease (IBD) is a chronic, recurring inflammation of the large intestine. In animal models and in studies of humans with the disease, a disrupted gut microbiota with an accumulation of potentially harmful organisms such as E. coli and other bacteria has been associated with IBD. Researchers have also observed that individuals with IBD have more bacteria associated with in?ammation and fewer bacteria with anti-in?ammatory traits.5,7
2. Irritable bowel syndrome
Irritable bowel syndrome (IBS) is a common, chronic disorder characterized by abdominal pain and altered bowel patterns, such as diarrhea or constipation or alternating symptoms of both. A growing body of research connects gut microbiota with IBS – in particular, how material passes through the cells of the intestinal lining, how gut muscles contract to move material (peristalsis), and how the body responds to pain from the gut.5,6
Compared to healthy individuals, those with IBS may have higher counts of some specific types of bacteria (Ruminococcaceae and Clostridium cluster XIVa) and lower counts of others (Bacteroides).
So far this is only a correlation – the debate is still open as to cause and effect. However, when one research team colonized germ-free rats with the microbiota from individuals with IBS, the rats experienced more abdominal contractions, a common IBS symptom.5 This suggests bacterial composition might be contributing to pain in IBS.
3. C. difficile infection
C. difficile bacteria are found throughout the environment, and a small number of individuals naturally carry the bacteria in their large intestine. For most individuals, a balanced microbiota keeps this potentially harmful population in check. However, a disruption of the gut microbiota can lead to unchecked growth of C. difficile. Usually this infection will cause diarrhea and abdominal cramping, but severe cases can lead to inflammation, bleeding, and even serious swelling of the colon that could cause it to rupture (toxic megacolon).9
C. difficile infection can be difficult to cure. In 15-30 percent of cases, the infection recurs at least once after treatment, and of these, 40-60 percent have more than one recurrence despite treatment.3,10 To help treat these difficult cases, patients can be given a microbiota (fecal) transplant to replace the imbalanced microbiota with healthy microbiota from a donor.
In one study, researchers gave 16 patients with persistent C. difficile infection standard treatment with the antibiotic vancomycin, followed by a flushing of the bowel and a microbiota transplant. The researchers gave a second group the antibiotic alone, while a third group received the antibiotic and bowel wash with no transplanted microbes.11
After 10 weeks, nine of 13 participants who received the antibiotic alone experienced a recurrence. Those who received both the antibiotic and bowel wash fared a bit worse, with 10 of 13 having a recurrence. However, the transplant treatment healed 13 of 16 participants who received it, and a second transplant cured two of the remaining three.
What’s more, after transplantation, the recipients' bacterial diversity resembled that of the healthy donors, with an increase in beneficial bacteria and a decrease in harmful bacteria.11 Other studies have achieved similar results, with a nearly 90-percent overall cure rate.
Fecal transplantation is recommended for individuals who have had multiple recurrences of C. difficile that didn’t improve with antibiotic treatment.12 Safety concerns remain, however, because of the risk that hidden harmful viruses, fungi, or bacteria could be transferred from one person to another.
The American Gastroenterology Society has launched a national registry to assess short-term and long-term outcomes associated with fecal transplantation and to determine its long-term safety.13 And researchers are working on ways to refine and target the delivery of beneficial microbiota.3
4. Colorectal cancer
Changes in the structure and metabolism of the gut microbiota possibly contribute to the development of colorectal cancer, which annually kills more than 800,000 people worldwide.14 Researchers believe that microbes in the gut can damage DNA by:
- Increasing cell growth
- Altering how stem cells develop
- Generating metabolites that contribute to gene mutations
The gut microbiota can either restrain or promote tumor growth by changing how the immune system monitors and regulates cells.15
Research suggests that diets high in saturated fat, commonly found in red and processed meats, are strongly connected to an increased risk for colorectal cancer.
One study found that individuals who ate this diet had lower concentrations of short-chain fatty acids (butyrate, acetate, propionate) than did other populations. Other studies have shown that individuals with colorectal cancer in general have lower concentrations of short-chain fatty acids.5
5. Intestinal permeability
The intestines are lined with a barrier designed to absorb nutrients and fluids while keeping pathogens out of circulation. Microbiota disruptions can lead to an increased ability of compounds such as endotoxins to penetrate or permeate this barrier.
These compounds can activate inflammatory and immune responses that worsen permeability. This condition can result in higher susceptibility to illness, less nutrient absorption, and gastrointestinal distress.
Research suggests that a low-fiber diet can change gut microbiota activity, leading to damage to the barrier layer of the intestines and increased permeability.16,17 Conversely, eating plenty of high-fiber foods – vegetables, fruits, whole grains, legumes, nuts, and seeds – help protect the intestinal barrier.17
Shifting the balance
In the past, most medical research focused on eliminating harmful bacteria through the development and use of antibiotics. But today, researchers are trying another strategy: promoting healthy bacteria in the gut.
Probiotics are live organisms that help maintain or restore balance within the microbiota. Perhaps the best-known probiotic source is yogurt, which, assuming it’s good quality, contains live bacteria that benefit health.
As investigators learn more about which types of bacteria maintain balance in the gut and which contribute to disease, they can explore ways to shift the makeup of bacterial populations to improve health. For instance, in Crohn’s disease, it is thought the bacteria F. prausnitzii is beneficial.5
Probiotics have also shown some promise in fighting colorectal cancer. In small clinical trials, researchers found that bacteria from the Lactobacillus genus reduced the concentration of a type of disease-causing bacteria in people with colorectal cancer and suppressed tumor growth for 2-4 years after treatment.15
The gut microbiome is a promising area of research when it comes to understanding and treating gastrointestinal diseases. More and more studies are finding strong connections between specific disorders and the makeup of the microbiome.
But this research is still fairly new, and the hard work is just beginning, because the gut microbiome is one of the most complex environments in the human body. Still, many scientists believe that understanding its intricacies will lead to new treatments and possible cures for many diseases.
- Rich R, ed. The microbiota in immunity and inflammation. In: Clinical Immunology: Principles and Practice. 5th ed. St. Louis, Mo.: Elsevier; 2019. https://www.clinicalkey.com. [Accessed August 1, 2019.]
- Said H, ed. Diet effects on gut microbiome composition, function, and host physiology. In: Physiology of the Gastrointestinal Tract. 6th ed. San Diego, Calif.: Elsevier; 2018. https://www.clinicalkey.com. [Accessed August 1, 2019.]
- Shin J, Warren C. Prevention and treatment of recurrent Clostridioides difficile infection. Curr Opin Infect Dis 2019;32:1-8.
- Almeida A, Mitchell A, Boland M, et al. A new genomic blue print of the human gut microbiota. Nature 2019;568:499-518.
- Nagao-Kitamoto H, Kitamoto S, Kuffa P, et al. Pathogenic role of the gut microbiota in gastrointestinal diseases. Intest Res 2016;14:127-138.
- Francino M. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol 2016;6:1-11.
- Ramos G, Papadakis K. Mechanisms of disease: inflammatory bowel diseases. Mayo Clin Proc 2019;94:155-165.
- Pittayonon R, Lau J, Yuan Y, et al. Gut microbiota in patients with irritable bowel syndrome – a systematic review. Gastroenterology 2019; 157:97-108.
- Clostridium difficile-induced diarrhea. Merck Manual Professional Version. https://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridium-difficile-induced-diarrhea. [Accessed July 31, 2019]
- Hopkins R, Wilson R. Treatment of recurrent Clostridium difficile colitis: a narrative review. Gastroenterol Rep 2018;6:21-28.
- Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407-415.
- McDonald L, Gerding D, Johnson S, et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Health Care Epidemiology of America (SHEA). Clin Infect Dis 2018;66:e1-e48.
- American Gastroenterological Association. Fecal Microbiota Transplantation National Registry. https://www.gastro.org/research-and-awards/registries-and-studies/fecal-microbiota-transplantation-fmt-national-registry. [Accessed July 31, 2019]
- Internal Agency for Research on Cancer. Cancer Fact Sheets: Colon 2018. http://gco.iarc.fr/today/fact-sheets-cancers . [Accessed July 31, 2019]
- Abreu M, Peek R. Gastrointestinal malignancy and the microbiome. Gastroenterology 2014;146:1534-1546.
- Desai M, Seekatz A, Koropatkin N, et al. A dietary-fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 2016;167:1339-1353.
- Llewellyn S, Britton G, Contijoch E, et al. Interactions between diet and the intestinal microbiota alter intestinal permeability and colitis severity in mice. Gastroenterology 2018;154:1037-1046.
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