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It is estimated that between 14,000 to 30,000 Americans die each year from Clostridium difficile infections. So finding a bacteria that could protect people from C. difficile is a big deal. However, it is only one bacteria, and sick people typically are depleted of a microbial community, not just one bacteria. From Science News:

Harmless bacterium edges out intestinal germ

Gut infections from the bacterium Clostridium difficile can be fought with a closely related but harmless microbe known as C. scindens. The friendly bacterium combats infection in mice by converting molecules produced in the liver into forms that inhibit C. difficile growth,researchers report October 22 in Nature.

C. scindens also appears to protect people from infection, the researchers found in a preliminary study in humans. The new findings could begin a path to the next generation of therapies using gut bacteria, says Alexander Khoruts, a gastroenterologist at the University of Minnesota in Minneapolis.

People who become infected with C. difficile typically have taken antibiotics, which wipe out the beneficial microbes in the gut, giving C. difficile a chance to take root. The infection can lead to cramps, diarrhea and even death. An estimated 500,000 to 1 million people get C. difficile infections each year in the United States. People with C. difficile receive more antibiotics to treat the infection or a fecal transplant to restore healthy microbes to the gut.

Several research groups have been trying to identify gut bacteria that are resilient in the face of C. difficile so that physicians can give patients those bacteria as a treatment, says Eric Pamer, an immunologist at Memorial Sloan Kettering Cancer Center. Single strains of bacteria such as C. scindens would offer significant advantages over fecal transplants: With a transplant, doctors screen the donated feces for pathogens that might sicken the recipient. But, Pamer says, “there are many things, viruses that have yet to be identified, that could be in a crude fecal product that might cause trouble.”  

Pamer and his team gave mice antibiotics to deplete beneficial microbes but not wipe them out completely. The researchers then fed the mice C. difficile spores and identified microbes that appeared in mice with lower amounts of C. difficile in their guts. C. scindens was the clear victor. It is harmless and present in most people, but in very low numbers.

The researchers also examined the microbial populations of 24 patients undergoing stem cell transplants. Those patients had lowered microbial diversity after receiving combinations of antibiotics, radiation and chemotherapy. The patients who didn’t develop C. difficile after the transplant were more likely to have C. scindens in their guts.

The researchers also investigated how C. scindens combats C. difficileC. difficile begins growing after it is exposed to certain molecules secreted in bile after a meal. However, another form of the molecule inhibits C. difficile growth. C. scindens transforms the molecule from one form to the other, boosting resistance to C. difficile.  

The possibilities are exciting. See my earlier posts on psychobiotics for more information. From Medical Xpress:

How gut bacteria ensures a healthy brain – and could play a role in treating depression

But medicine in the 21st century is rethinking its relationship with bacteria and concluding that, far from being uniformly bad for us, many of these organisms are actually essential for our health. Nowhere is this more apparent than in the human gut, where the microbiome  – the collection of bacteria living in the gastrointestinal tract - plays a complex and critical role in the health of its host.

The microbiome interacts with and influences organ systems throughout the body, including, as research is revealing, the brain. This discovery has led to a surge of interest in potential gut-based treatments for neuropsychiatric disorders and a new class of studies investigating how the gut and its microbiome affect both healthy and diseased brains.

The lives of the bacteria in our gut are intimately entwined with our immune, endocrine and nervous systems. The relationship goes both ways: the microbiome influences the function of these systems, which in turn alter the activity and composition of the bacterial community. We are starting to unravel this complexity and gain insight into how gut bacteria interface with the rest of the body and, in particular, how they affect the brain.

The microbiome-immune system link is established early on. Over the first year of life, bacteria populate the gut, which is largely sterile at birth, and the developing immune system learns which bacteria to consider normal residents of the body and which to attack as invaders. This early learning sets the stage for later immune responses to fluctuations in the microbiome's composition.

When a normally scarce strain becomes too abundant or a pathogenic species joins the community of gut bacteria, the resulting response by the immune system can have wide-reaching effects. Depression has been linked with elevated levels of such molecules in some individuals, suggesting that treatments that alter the composition of the microbiome could alleviate symptoms of this disorder.

Such an intervention could potentially be achieved using either prebiotics – substances that promote the growth of beneficial bacteria – or probiotics – live cultures of these bacteria. It is even possible that the microbiome could be manipulated by dietary changes.

In one experiment, researchers transplanted the human microbiome into germ-free mice (animals that have no gut bacteria) in order to study it in a controlled setting. They found that, simply by changing the carbohydrate and fat content of the mice's food, they could alter basic cellular functions and gene expression in the microbiome.

Depression is not the only psychiatric disorder in which the microbiome may play a role.Research in rodents, as well as a few preliminary studies in humans, indicate that the state of our resident microbes is tied to our anxiety levels.

This research also reveals the complexity of the relationship between the microbiome and psychological state. ...Researchers have shown that the presence or absence of microbes in young mice affects the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis – a key pathway in the body's stress response system. The activity of the microbiome during development thus sways how we respond to future stressors and how much anxiety they cause us.

How do the bacteria in our gut wield such influence over our brains and bodies? The mechanisms of microbiome-host interactions appear to be as numerous and varied as the interactions themselves.

Maybe bacteria are involved in Multiple sclerosis (MS). From Scientific American:

Could Multiple Sclerosis Begin in the Gut?

MS researchers are focusing on the content of the gut’s microbiome as a possible contributor to the body’s autoimmune attack on its nervous system.

Multiple sclerosis (MS) is an electrical disorder, or rather one of impaired myelin, a fatty, insulating substance that better allows electric current to bolt down our neurons and release the neurotransmitters that help run our bodies and brains. Researchers have speculated for some time that the myelin degradation seen in MS is due, at least in part, to autoimmune activity against the nervous system. Recent work presented at the MS Boston 2014 Meeting suggests that this aberrant immune response begins in the gut.

Eighty percent of the human immune system resides in the gastrointestinal tract. Alongside it are the trillions of symbiotic bacteria, fungi and other single-celled organisms that make up our guts’ microbiomes. Normally everyone wins: The microorganisms benefit from a home and a steady food supply; we enjoy the essential assistance they provide in various metabolic and digestive functions. Our microbiomes also help calibrate our immune systems, so our bodies recognize which co-inhabitants should be there and which should not. Yet mounting evidence suggests that when our resident biota are out of balance, they contribute to numerous diseases, including diabetes, rheumatoid arthritis, autism and, it appears, MS by inciting rogue immune activity that can spread throughout the body and brain.

One study presented at the conference, out of Brigham and Women’s Hospital (BWH), reported a single-celled organism called methanobrevibacteriaceae that activates the immune system is enriched in the gastrointestinal tracts of MS patients whereas bacteria that suppress immune activity are depleted. Other work, which resulted from a collaboration among 10 academic researcher centers across the U.S. and Canada, reported significantly altered gut flora in pediatric MS patients while a group of Japanese researchers found that yeast consumption reduced the chances of mice developing an MS-like disease by altering gut flora.

Sushrut Jangi, a staff physician at Beth Israel Deaconess Medical Center in Boston who co-authored the BWH study, thinks that regional dietary influences might even be at play. “The biomes of people living in different areas and who consume Western versus non-Western diets are demonstratively different,” he says. “People who emigrate from non-Western countries, including India, where MS rates are low, consequently develop a high risk of disease in the U.S. One idea to explain this is that the biome may shift from an Indian biome to an American biome,” although there is not yet data to support this theory.

The microbiome theory is gaining so much steam in academia that a coalition of four U.S. research centers called the MS Microbiome Consortium recently formed to investigate the role of gut microorganisms in the disease. The group presented data in Boston showing significantly different gastrointestinal bacterial populations in patients treated with the MS drug glatiramer acetate compared with untreated subjects. How exactly the drug suppresses MS activity is unknown but the findings suggest that perhaps it works in part by altering gut flora and, as a result, suppressing abnormal immune activity. “But important questions remain, such as how MS medications affect the microbiome, how an individual’s microbiome may affect treatment responses, whether particular bacterial species are associated with more severe disease and ultimately whether we can manipulate the microbiome to benefit our patients.”

Katz Sand says that dietary and probiotic approaches to treating MS are worth pursuing, as is a less palatable approach: fecal transplantation.Yet answers in science and medicine are rarely simple, she added, pointing out that in all likelihood MS arises from a complicated confluence of genetic and environmental influences that might ultimately trigger autoimmune activity. Beyond just our gut flora well over 100 genetic variants —many related to immune function—are now known to contribute to the disease as are external factors including vitamin D deficiency  (MS is more common at higher latitudes), smoking and increased salt intake. 

Improving gut bacteria is a good reason to eat apples. Take note that this study was done with mice, but the researchers think it also applies to humans. From Medical News Today:

Could an apple a day protect against obesity?

An apple a day may keep obesity away, particularly if it is of the Granny Smith variety, according to a new study from Washington State University.

Apples have many health benefits, according to previous research. Last year, Medical News Today reported on a study suggesting that eating an apple a day may be just as beneficial as daily statin use for preventing vascular mortality. A 2011 study also claimed that apples and pears may reduce the risk of stroke by more than 50%.

But according to the team involved in this latest research, very few studies have looked at how the bioactive compounds in apples that are not absorbed during digestion - such as polyphenols (a type of antioxidant) and dietary fiber - affect the friendly gut bacteria that boost immunity and aid weight maintenance.

With this in mind, Noratto and her team analyzed how the bioactive compounds of seven different varieties of apples - Granny Smith, Braeburn, Fuji, Gala, Golden Delicious, McIntosh and Red Delicious - affected the good gut bacteria of diet-induced obese mice. The researchers found that, compared with all other apple varieties, Granny Smiths appeared to have the most beneficial effect on good gut bacteria.

The balance of gut bacteria among obese people is usually impaired. But when comparing the feces of obese mice fed Granny Smiths with the feces of lean mice, the team found that the proportions of bacteria - specifically the presence of Firmicutes, Bacteroidetes, Enterococcus, Enterobacteriaceae, Escherichia coli and Bifidobacterium - were very similar.

The researchers explain that Granny Smiths are high in non-digestible dietary fiber and polyphenols, and low in carbohydrates. Even after chewing and exposure to stomach acid and digestive enzymes, the compounds are unscathed when they reach the colon. The bacteria present in the colon then ferment the compounds, producing butyric acid that spurs on the growth of friendly gut bacteria.

An imbalance of gut bacteria - determined by the food we eat - can cause chronic inflammation  that leads to diabetes. But the researchers say that re-establishing the balance of gut bacteria through consumption of Granny Smith apples may reduce such inflammation, as well as promote satiety.

Amazing possibilities, but more studies needed. The key finding: A diversity of the bacterial community in the gut is good, and perhaps can be altered through diet, and so perhaps alter the future risk of developing breast cancer.From Science Daily:

Diverse gut bacteria associated with favorable ratio of estrogen metabolites

Postmenopausal women with diverse gut bacteria exhibit a more favorable ratio of estrogen metabolites, which is associated with reduced risk for breast cancer, compared to women with less microbial variation, according to a new study.

Since the 1970s, it has been known that in addition to supporting digestion, the intestinal bacteria that make up the gut microbiome influence how women's bodies process estrogen, the primary female sex hormone. The colonies of bacteria determine whether estrogen and the fragments left behind after the hormone is processed continue circulating through the body or are expelled through urine and feces. Previous studies have shown that levels of estrogen and estrogen metabolites circulating in the body are associated with risk of developing postmenopausal breast cancer.

"In women who had more diverse communities of gut bacteria, higher levels of estrogen fragments were left after the body metabolized the hormone, compared to women with less diverse intestinal bacteria," said one of the study's authors, James Goedert, MD, of the National Institutes of Health's National Cancer Institute (NCI) in Bethesda, MD. "This pattern suggests that these women may have a lower risk of developing breast cancer."

As part of the cross-sectional study, researchers analyzed fecal and urine samples from 60 postmenopausal women enrolled in Kaiser Permanente Colorado. .

"Our findings suggest a relationship between the diversity of the bacterial community in the gut, which theoretically can be altered with changes in diet or some medications, and future risk of developing breast cancer," Goedert said. 

Two related articles, the first from a month ago, but both discuss eating fresh foods of summer and the effect on the microbiota. From Gut Microbiota Worldwatch:

Seasonal diet changes affect the composition of our gut microbiota

The mix of bacteria that live in our gut changes throughout the year, to match the food we eat in every specific season. For example, bacteria that process fresh fruit and vegetables are more abundant in the summer, and those that process fats are mode abundant in winter times. A group of scientists at the University of Chicago has found evidence of this seasonal shift in the gut flora, by studying the remote Hutterite population, in North America. The traditional diet and common meals of this community have allowed researchers to study the effect of one common diet in a large population over a long period of time.

Hutterites live in communal farms (colonies) and eat meals in common dining rooms, using traditional recipes that have been relatively stable over time and between colonies. They have little contact with the world outside their colonies, which translates into a very homogeneous genetic pool. Sixty Hutterites from six colonies answered questionnaires about what they ate over the course of a year. During the same period, scientists sampled their stool periodically, to find the genetic sequences of bacteria contained in their gut.

The Hutterites’ diet is relatively stable, except that in summer they eat more fresh fruit and vegetables, and in winter they eat less, and turn to frozen or canned food. Remarkably, their gut flora responded to these changes with massive modification in the abundance of certain bacteria. For example, during summer Bacteroidetes were more abundant: this group of bacteria contain complex carbohydrate digesters, which may be at work in processing fresh fruit and vegetables.

On the other hand Actinobacteria increased in winter: these microbes are associated with processing fat, and with a decreased content of fibre in food. Researchers also found seasonal shifts in other types of bacteria, whose associations with food are still unknown. Notably, the trends were almost identical in all six colonies, possibly a result of a very homogenous lifestyle carried on in a very similar environment.

Although Hutterites live in a relatively isolated way, they use technology and medicine, which makes their lifestyle closer to the general population than that of other more traditional communities. That is why the authors believe that these results may be extended to the general population.

This healthy living article promotes eating fresh fruits and vegetables (tomatoes, blueberries, asparagus, and leeks) as good for the gut microbiome. From Huffington Post:

4 Summer Foods That Can Help Trim Your Waist

We know so little about the viruses in the human microbiome that a study just reported a newly discovered gut virus found in most of the world's population. From Medical Xpress:

Newly discovered gut virus lives in half the world's population

Odds are, there's a virus living inside your gut that has gone undetected by scientists for decades. A new study led by researchers at San Diego State University has found that more than half the world's population is host to a newly described virus, named crAssphage, which infects one of the most common types of gut bacteria, Bacteroidetes. This phylum of bacteria is thought to be connected with obesity, diabetes and other gut-related diseases.

The fact that it's so widespread indicates that it probably isn't a particularly young virus, either. "We've basically found it in every population we've looked at," Edwards said. "As far as we can tell, it's as old as humans are." He and his team named the virus crAssphage, after the cross-assembly software program used to discover it.

Some of the proteins in crAssphage's DNA are similar to those found in other well-described viruses. That allowed Edwards' team to determine that their novel virus is one known as a bacteriophage, which infects and replicates inside bacteria—and using innovative bioinformatic techniques, they predicted that this particular bacteriophage proliferates by infecting a common phylum of gut bacteria known as Bacteriodetes.

 Further details about crAssphage have been difficult to come by. It's unknown how the virus is transmitted, but the fact that it was not found in very young infants' fecal samples suggests that it is not passed along maternally, but acquired during childhood.

A big benefit to exercising - more microbial diversity, which means a healthier gut microbiome, which means better health. From Medscape:

Exercise Linked to More Diverse Intestinal Microbiome

Professional athletes are big winners when it comes to their gut microflora, suggesting a beneficial effect of exercise on gastrointestinal health, investigators report in an article published online June 9 in Gut.

DNA sequencing of fecal samples from players in an international rugby union team showed considerably greater diversity of gut bacteria than samples from people who are more sedentary.

Having a gut populated with myriad species of bacteria is thought by nutritionists and gastroenterologic researchers to be a sign of good health. Conversely, the guts of obese people have consistently been found to contain fewer species of bacteria, note Siobhan F. Clarke, PhD, from the Teagasc Food Research Centre, Moorepark, Fermoy. "Our findings show that a combination of exercise and diet impacts on gut microbial diversity. In particular, the enhanced diversity of the microbiota correlates with exercise and dietary protein consumption in the athlete group," the authors write.

The investigators used 16S ribosomal RNA amplicon sequencing to evaluate stool and blood samples from 40 male elite professional rugby players (mean age, 29 years) and 46 healthy age-matched control participants. 

Relative to control participants with a high BMI, athletes and control participants with a low BMI had improved metabolic markers. In addition, although athletes had significantly increased levels of creatine kinase, they also had overall lower levels of inflammatory markers than either of the control groups.

Athletes were also found to have more diverse gut microbiota than controls, with organisms in approximately 22 different phyla, 68 families, and 113 genera. Participants with a low BMI were colonized by organisms in just 11 phyla, 33 families, and 65 genera, and participants with a high BMI had even fewer organisms in only 9 phyla, 33 families, and 61 genera.

The professional rugby players, as the investigators expected, had significantly higher levels of total energy intake than the control participants, with protein accounting for 22% of their total intake compared with 16% for control participants with a low BMI and 15% for control participants with a high BMI. When the authors looked for correlations between health parameters and diet with various microbes or microbial diversity, they found significant positive association between microbial diversity and protein intake, creatine kinase levels, and urea.

Another article reporting on the Crohn's disease study I posted yesterday. But this article lists the depleted bacteria and also which ones there are too much of in Crohn's patients. It illustrates that gut microbial communities being out of whack go hand in hand with disease. Remember: dysbiosis means an imbalance in the microbial populations. Interestingly, just like in the 2012 sinusitis study (see my December 4, 2013 post) - it's biopsies that found the specific bacterial imbalances, and not fecal samples or mucus/phlegm swabs (typically done in sinusitis). Big step forward in human microbiome research. And again antibiotics are not the answer.

From Science magazine:

Crohn's Disease Marked by Dramatic Changes in Gut Bacteria

The largest clinical study of its kind is revealing new insights into the causes of Crohn's disease, a periodic inflammation of the intestines. The research, which involved 668 children, shows that numbers of some beneficial bacteria in the gut decrease in Crohn's patients, while the number of potentially harmful bacteria increases. The study could lead to new, less invasive diagnostic tests; it also shows that antibiotics—which aren't recommended for Crohn's but are often given when patients first present with symptoms—may actually make the disease worse.

Crohn’s disease is one of the two major inflammatory bowel diseases (IBDs); the other is ulcerative colitis, a similar condition that affects only the colon. Both have been on the rise in the developing world since the early 1950s; now, an estimated 1.4 million people suffer from IBD in the United States alone. Symptoms include diarrhea, abdominal pains and cramping, and intestinal ulcers.

But genes alone can't explain the sharp rise in IBD incidence, and scientists have looked at the environment—in particular diet and antibiotic use—for answers.

Several studies have shown that Crohn’s disease is characterized by microbial dysbiosis, a shift in the microbial populations inhabiting the gut, but it's difficult to unravel cause and effect: A change in gut microbiota can cause inflammation, but the reverse can also occur. Complicating the picture is the fact that before being diagnosed with IBD, patients often receive antibiotics to fend off a supposed gut infection that could be causing the symptoms, which also have a powerful impact on the microbial populations living in our guts.

Now, a group headed by Ramnik Xavier, a gastroenterologist at Harvard Medical School in Boston, has collected fecal samples and taken biopsies of the lower part of the small intestine and rectum from 447 children who had just been diagnosed with Crohn's, and a control group of 221 kids who had noninflammatory abdominal symptoms, such as bloating and diarrhea. In contrast with previous studies, the majority of patients had not yet received antibiotics or anti-inflammatory drugs. Based on their genetic material, the researchers determined the relative abundance of a range of microbial species in the samples.

Some potentially harmful microbial species were more abundant in Crohn's patients, such as those belonging to the Enterobacteriaceae, Pasteurellaceae, Veillonellaceae, and Fusobacteriaceae; numbers of the ErysipelotrichalesBacteroidales, and Clostridiales, generally considered to be beneficial, were lower. The disappearance and appearance of species can be equally important, says Dirk Gevers of the Broad Institute in Cambridge, Massachusetts, who performed most of the work. "There has been a shift in the ecosystem, which affects both types.”

But those differences were found mostly in the biopsy samples; there weren't many differences between the feces from Crohn's patients and the control group. At this early stage of the disease, "the dysbiosis seems not to have reached the stool yet," Gevers says.

The dysbiosis was also more pronounced in patients who had received antibiotics. "This study confirms that these drugs don’t do any good to people with Crohn’s disease," says gastroenterologist Séverine Vermeire of the Catholic University of Leuven in Belgium, who was not involved in the study. "We knew antibiotic use increases the risk to develop the disease; now we know they can worsen it, too."

Vermeire says it's a "missed opportunity" that the researchers didn't look at the patients' diets. "That could have helped elucidate why this disease occurs so much more in the Western world than elsewhere." In 2011, Vermeire’s group published a study showing that healthy family members of Crohn's disease patients have a slight dysbiosis as well. Vermeire is convinced that even in these families, it's not genetics but some lifestyle factor that causes the phenomenon. "If we could identify the dysbiosis in an early stage, and we knew the causative factors,” she says, “we could prevent disease occurrence by bringing about lifestyle changes.”

Two related studies showing the importance of the intestinal bacterial community for health and preventing diseases. Both also discuss how antibiotics disrupt the gut microbial community. From Science Daily:

Microbes help to battle infection: Gut microbes help develop immune cells, study finds

The human relationship with microbial life is complicated. Although there are types of bacteria that can make us sick, Caltech professor of biology and biological engineering Sarkis Mazmanian and his team are most interested in the thousands of other bacteria -- many already living inside our bodies -- that actually keep us healthy. Now, he and his team have found that these good bugs might also prepare the immune cells in our blood to fight infections from harmful bacteria.

In the recent study, published on March 12 in the journal Cell Host & Microbe, the researchers found that beneficial gut bacteria were necessary for the development of innate immune cells -- specialized types of white blood cells that serve as the body's first line of defense against invading pathogens.

In addition to circulating in the blood, reserve stores of immune cells are also kept in the spleen and in the bone marrow. When the researchers looked at the immune cell populations in these areas in so-called germ-free mice, born without gut bacteria, and in healthy mice with a normal population of microbes in the gut, they found that germ-free mice had fewer immune cells -- specifically macrophages, monocytes, and neutrophils -- than healthy mice. Germ-free mice also had fewer granulocyte and monocyte progenitor cells, stemlike cells that can eventually differentiate into a few types of mature immune cells

Khosravi and his colleagues next wanted to see if the reduction in immune cells in the blood would make the germ-free mice less able to fight off an infection by the harmful bacterium Listeria monocytogenes -- a well-studied human pathogen often used to study immune responses in mice. While the healthy mice were able to bounce back after being injected with Listeria, the infection was fatal to germ-free mice. When gut microbes that would normally be present were introduced into germ-free mice, the immune cell population increased and the mice were able to survive the Listeria infection.

The researchers also gave injections of Listeria to healthy mice after those mice were dosed with broad-spectrum antibiotics that killed off both harmful and beneficial bacteria. Interestingly, these mice also had trouble fighting the Listeria infection. "We didn't look at clinical data in this study, but we hypothesize that this might also happen in the clinic," says Mazmanian. "For example, when patients are put on antibiotics for something like hip surgery, are you damaging their gut microbe population and making them more susceptible to an infection that had nothing to do with their hip surgery?"

More importantly, the research also suggests that a healthy population of gut microbes can actually provide a preventative alternative to antibiotics, Khosravi says. 

From Science Daily:

Large study identifies exact gut bacteria involved in Crohn's disease

While the causes of Crohn's disease are not well understood, recent research indicates an important role for an abnormal immune response to the microbes that live in the gut. In the largest study of its kind, researchers have now identified specific bacteria that are abnormally increased or decreased when Crohn's disease develops. The findings, which appear in the March 12 issue of the Cell Press journal Cell Host & Microbe, suggest which microbial metabolites could be targeted to treat patients with this chronic and currently incurable inflammatory bowel disease.

Twenty-eight gastroenterology centers across North America have been working together to uncover how microbes contribute to the inflammatory cascade of Crohn's disease. Researchers took biopsies from 447 individuals with new-onset Crohn's disease and 221 nonaffected individuals at multiple locations along the gastrointestinal tract and then looked for differences between the two groups. They also validated their methods in additional individuals, resulting in a total of 1,742 samples from pediatric and adult patients with either new-onset or established disease.

The team found that microbial balance was disrupted in patients with Crohn's disease, with beneficial microbes missing and pathological ones flourishing. Having more of the disease-associated organisms correlated with increasing clinical disease activity. 

When the researchers analyzed the effects of antibiotics, which are sometimes used to treat Crohn's disease symptoms prior to diagnosis, they found that antibiotic usage in children with Crohn's disease could be counterproductive because it causes a loss of good microbes and an increase in pathological ones.