The microbiome affects celiac severity in mice

In non-celiac people, gluten is broken down into its constituent proteins and does not elicit any immune response.  In celiac disease, however, the gluten proteins cause inflammation, which can result in a number of GI issues.  The microbiome has long been thought to play a role in this disease, because of its importance to immune mediation, and its role in gluten breakdown.  An international group of scientists recently tested the role of various different characteristic microbiome communities on the immune reaction in mice with celiac disease.  They published their results last week in the American Journal of Pathology.

The scientists used a mouse model for celiac disease that involved genetically modified mice that had an immune response to gluten.  They split the mice into three groups, one group had a typical healthy microbiome, the next had a healthy microbiome but without proteobacteria, and the final group was germ free (i.e. completely lacking a microbiome).  When the germ free mice were challenged with gluten they had the highest inflammatory response.  This included increases in immune cells, and breakdown of the intestinal villi.  Unsurprisingly, when the germ free mice were colonized with normal microbiota, their inflammatory response was attenuated.   The scientists then discovered an important relationship between celiac’s and Proteobacteria.  The mice that harbored this phylum had more severe responses to gluten, suggesting that these bacteria somehow worsen the inflammatory response to gluten.  Antibiotic treatment that increased the amounts Proteobacteria, and the relative abundances of Escherichia, Helicobacter, Pasteurella, and Lactobacillus, also increased the inflammatory response.

The exact mechanisms by which the microbiome are mediating the immune response are unclear.  Bacteria are known to induce various immune cells and also break down gluten, and these mechanisms may be involved.  In either case gluten sensitivity and celiac disease are clearly affected by the microbiome.

Does the use of antibiotics for bacterial vaginosis during pregnancy reduce the risk of preterm birth?

Bacterial vaginosis (BV) is an inflammatory disease that is defined as a vaginal microbiome that is not dominated by Lactobacilli.  This abnormal vaginal flora is associated with preterm birth and miscarriage.  A recent study showed that women’s vaginal microbiomes shift frequently during pregnancy, but that the amount of time spent with a flora not dominated by Lactobacillus was associated with the length of the pregnancy, i.e. the less time spent with Lactobacillus the shorter the pregnancy.  Considering these studies, doctors may want to begin screening the vaginal microbiome during pregnancy, and treating BV (which is currently done through antibiotics).  Strategies such as that one have not yet been rigorously studied, so their efficacy is still unknown.  Last week a study out of Japan performed a study that showed little improvement in preterm birth risk by monitoring and treating BV during pregnancy.  The results were published in Nature Scientific Reports.

The researchers measured the microbiomes of 1,735 pregnant women and split them into two groups.  Women in the intervention group that had BV were given antibiotics, whereas women in the control group, whether they had BV or not, proceeded as normal through their pregnancy.  Women in both groups had their vaginal microbiomes sampled at various time points throughout the pregnancy. The first group would have their BV status verified, and placed on antibiotics. In both groups, approximately 10% of the women had preterm birth at around 30 weeks gestational age.  There was no significant difference in these rates between the two groups, meaning that administration of antibiotics did not appear to prevent preterm birth.  Even though the antibiotics did not prevent preterm birth, the researchers noted that regardless of group, women who entered preterm birth did have abnormal vaginal flora compared to women who went full term, supporting the notion that BV is highly correlated with preterm birth.  They noted that many of the women who entered preterm labor did not have BV at the initial time of screening, but acquired BV at some point during pregnancy. 

This paper supports the idea that BV may cause preterm birth, however it cannot recommend universal screening for BV in pregnant women for two reasons.  First, the antibiotics did not appear to affect the rates of preterm birth, and second many of the women who had preterm birth only had abnormal flora after initial screening.  Perhaps a better strategy would be to constantly monitor BV status throughout pregnancy.  In addition, there will soon be healthier and more effective methods to treat BV than antibiotics, which are only shown to have a transient effect on BV and disrupt the rest of the microbiome.

The effect of various treatments for juvenile Crohn’s disease on the microbiome

CT scan showing Crohn's disease in the fundus of the stomach

Crohn’s disease is a type of inflammatory bowel disease that is characterized by an autoimmune response in the colon.  It is generally thought that the bacteria in the gut elicit this immune response and cause the disease.  In otherwords, Crohn’s is caused by a shift in the microbiome from a healthy state, to a dysbiotic one, although the ultimate cause of the disease is still unknown.  The standard of care for Crohn’s in adults is combinations of immunosuppressive drugs, although in children this is not normally recommended.  Instead, children take either a prescribed diet, normally something like Soylent that involves only essential nutrients, or antibiotics.  Scientists from UPenn recently monitored the microbiomes of children with Crohn’s that were put on various courses of treatment, as well as the progression of the disease.  They discovered the changes that occurred in the microbiome that yielded a therapeutic response, and many new associations between the microbiome and Crohn’s disease.  They published their results in Cell Host and Microbe.

The scientists measured the microbiomes and inflammatory markers of 90 children before and after entering therapy for Crohn’s: 52 taking anti-TNF (an immunosuppressant), 22 taking the enteral nutrition exclusively (i.e. something like soylent), and 16 taking the enteral nutrition along with any other food they wanted.  The scientists also took samples from 26 healthy children.  They discovered that of the 45 most abundant bacteria in each child, 14 were different between the Crohn’s children and the healthy children.  These included bacteria such as Prevotella and Odoribacter that were largely absent from the Crohn’s group, and Streptococcus, Klebsiella, and Lactobacillus that were in higher abundances in the diseased group.  Overall diversity was also higher in healthy patients compared to those with Crohn’s.  The researchers also discovered that high levels of fungi, such as Saccharomyces cerevisiae, in the stool were high associated with Crohn’s.  When the researchers monitored the response of Crohn’s patients to treatment they saw that in many patients the microbiome shifted rapidly to a healthier state, with less inflammation, within a week of treatment for all three therapies involved.

This study helped further define the dysbiosis that is associated with Crohn’s disease, as well as demonstrate how this dysbiosis is altered using treatment.  It was especially useful that treatment naïve children were used in the study, as many adult studies are unable to remove confounding variables of various previous courses of treatments.  IBD is a difficult disease to study because of its complexity, but this study supports the hypothesis that a dysbiosis is at the root of the problem.

Red wine and coffee modulate the microbiome

Prebiotics are foods that alter the microbiome.  They are important to many potential microbiome therapeutics because they could be used to shift the microbiome from a dysbiotic, or unhealthy state, to a normal healthy state.  Most scientists that study prebiotics investigate indigestible fiber, because these are known to survive digestion are broken down by specific microbes, thus predictably selecting for specific organisms’ growth.  Recently though, other prebiotics are being studied.  A major class of these are polyphenolic compounds, which provide the antioxidant characteristics of plant material.  Last week researchers from Spain studied the shift in the microbiome that may be induced by red wine and coffee in particular.  They published their results in the journal Food & Function.

The researchers studied 23 patients that had allergic rhinosinusitis or asthma as well as 22 age-matched controls.  They chose individuals with autoimmune diseases because of the promise of prebiotics affecting their diseases.  They asked all of the individuals to fill out a food survey of what they had eaten in the past year, and how often they ate it.  After, the scientists took samples of their feces and measured the bacteria within it.  The scientists found that the abundance of Clostridium, Lactococcus and Lactobacillus was directly associated with polyphenol intake from coffee, and that Bacteroides was positively associated with red wine consumption.  Unfortunately, they noted that these did not differ between allergic people and healthy ones.

This study was certainly lacking in its scope and rigor.  It did not attempt any interventional studies to controllably reproduce these effects, and it did not identifiy specific polyphenols that are responsible.  Nonetheless, it does begin to define how alternative prebiotics may affect our microbiome.  Polyphenols in particular are linked to all sorts of health benefits, normally attributed to their anti-oxidation, however perhaps they positively impact the microbiome as well. 

Clinical trial for probiotics in irritable bowel syndrome fails to show efficacy

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting about 10-15% of people in the United States alone, according to the International Foundation for Functional Gastrointestinal Disorders website. Fortunately, as described by the IFFGD, IBS is a functional disorder, meaning that while it does affect quality of life, it does not affect life expectancy. Probiotics have been studied as treatment for IBS because, as we’ve seen in many other examples of probiotic use, it is safe and rarely has any negative effects on the consumer. Some trials have shown that probiotics help relieve the symptoms of IBS; however the conclusions are controversial due to study structure and participant numbers. For this reason, scientists in Seoul, South Korea recently published a study in the Journal of Clinical Biochemistry and Nutrition, which studied the effects of a multi-species probiotic mixture on IBS symptoms using a double-blind study with a large number of participants.

Eighty-one patients participated in the 4-week-long double-blind study, with 42 people receiving a multi-species probiotic (containing Lactobacilli, Bifidobacteria, and Streptococci) and 38 people receiving a placebo. Baseline fecal samples were collected before probiotic/placebo consumption, revealing no significant difference between the two groups of participants. After consumption, the probiotic group showed a significant increase in concentrations of the probiotic bacterial strains in fecal samples, but not significant increase of levels of Bacteroidetes and Firmicutes.

In terms of symptom relief, while the probiotic group reported a greater percentage of relief, it was not significantly greater than the placebo group. This could be a classic case of the placebo effect, which is a phenomenon in which a sham treatment can actually improve symptoms because the person receiving the placebo believes it will help them. The results of this study are not concrete because there was no significant difference in symptom improvement; however there were significant increases in probiotic strains in fecal samples of the probiotic group. This study could be a step in the right direction toward relieving IBS symptoms.

Vaginal microbiome once again tied to preterm birth

Preterm birth is major global health challenge.  Today, around 11% of all babies are born prior to 37 weeks, and are considered preterm.  Many of the causes of these preterm births are still unknown, but it is thought that around 25% of them may be related to a bacterial infection that comes from somewhere in the mother’s own body, i.e. her microbiome.  Many studies are now linking specific vaginal bacteria to risk of preterm birth, and other studies have even shown a connection between other microbiome sites, such as the gut and oral microbiome.  Unfortunately, studies on the microbiome and preterm birth are extremely difficult to conduct, so there are just not enough to have any sort of scientific consensus on the topic.  Last week though, a very rigorous study out f Stanford University was published in the Proceedings of the National Academy of Sciences that monitored expectant mothers vagina, gut, and oral microbiome throughout the course of her pregnancy and then for one year after.  Among many interesting findings, which are discussed below, the most important one was yet another connection between bacterial vaginosis and preterm birth.

The researchers monitored the vaginal, distal gut, salivary, and tooth/gum microbiomes of 49 women, 15 of which ended up delivering preterm, over the course of their pregnancy and for one year after.  Interestingly, the non-vaginal sites’ microbiomes remained relatively stable over the duration of the pregnancy, and even for the one year after.  The vaginal microbiome, however, did show some differences during and after pregnancy.

As many of our readers already know, a healthy vaginal flora is dominated by Lactobacilli, but around 20% of American women are dominated by other species, such as Gardnerella vaginalis, and have an overall increased vaginal diversity.  These women have what is known as community state type four, or CST4, and these women could be diagnosed with bacterial vaginosis (BV), though the clinical diagnosis is not so specific.  The other community state types, CST1, 2, 3, and 5, are dominated by different strains of Lactobacilli, and are generally regarded as healthy.  This current research showed that many of the women’s vaginal microbiomes actually shifted between various CST’s during pregnancy, most often shifting to and from CST4.  These transitions had no association with preterm birth, though.  After giving birth the vaginal microbiome became more diverse, and had greater abundances in anaerobic bacteria, such as Peptoniphilus, Prevotella, and Anaerococcus.  In addition, this usually coincided with a decrease in Lactobacilli.  Surprisingly, these changes did not seem to relate to mode of delivery (C-section of vaginal).

CST4 has been linked to preterm birth before, and this was reinforced in this study.  The scientists found that the longer a women’s vaginal microbiome was within CST4, the greater risk she had for preterm birth.  In addition, the abundance of Gardnerella and Ureaplasma, specifically, were linked to preterm birth.

This study reinforces what many microbiome scientists already suspect, and that is the importance of the vaginal flora in preterm birth.  It is unclear at this point if manipulating the vaginal flora prior to, or during pregnancy would help prevent preterm birth, but it is certainly worthy of discussion and clinical testing.  If you are reading this and wondering what your vaginal microbiome is, then we recommend you participate in the citizen science project, YourPrivateBiome, to find out.  You can learn more about it by following this link on our site, or just click the link above.