The microbiome can modulate helminth-mediated allergic inflammation

We’ve talked about how helminths can impact health, highlighting many studies that describe relationships between helminth infections, disease, and industrialization versus underdevelopment.  Asthma is a condition prevalent particularly in industrialized/westernized societies, and helminths have been shown to directly regulate immune responses and are linked with a reduction in asthma prevalence.  Correspondingly, there is less incidence of asthma in underdeveloped societies.  Additionally, helminth infections are typically associated with compositional shifts in intestinal microbiota.  A large research team sought to investigate the potential role of intestinal microbiota in modulating helminth-induced allergic inflammation, postulating that there is indeed significant cross-talk between the microbiome and helminths as opposed to intrinsic inflammatory responses to helminths. 

The researchers first determined that helminth infection can reduce the severity of allergic airway inflammation in mice.  Mice were infected with Heligmosomoides polygyrus bakeri (Hpb) murine-specific helminths and then exposed to house dust mite to induce allergic inflammation.  The mice exposed to the Hpb helminth demonstrated a reduction in severity of inflammation.  Next, the researchers were able to demonstrate that intestinal bacteria play a role in helminth’s modulatory role of allergic airway inflammation.  Antibiotics were administered to Hpb-infected mice to eliminate intestinal microbiota populations.  Helminths infection reduced inflammation, but did not attenuate inflammation in anti-biotic treated mice, even though total worm-count was similar between both groups (antibiotic group and non-antibiotic group). 

Helminth exposure and subsequent shifts in microbiota composition and biochemical activity was then examined.  16S sequencing revealed that Hpb-infected mice induced an outgrowth of Clostridiales bacteria.  Increases in small-chain fatty-acid (SCFAs) were also observed in Hpb-infected mice, a likely outcome of a shift in bacterial community structure.  Interestingly, the microbiota of a Hpb-infected mice were transferred to naïve mice, and this was sufficient in protecting against allergic inflammation, further confirming the microbiome’s modulatory roles.  Previous reports have pointed to regulatory T cells (Tregs) as responsible for regulating immune/inflammatory responses, and in this study the researchers demonstrated Treg involvement.  Furthermore, helminth-induced Treg suppression and anti-inflammatory activity was observed, mediated by a G-protein receptor entitled GPR-41. 

Together these findings further elucidate the role of helminths in disease, while uniquely pointing to the gut microbiome as a critical mediator of this interaction.  Learning more about these relationships can help us better understand broad epidemiology trends associated with helminth infection and human health.  

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Microbiome in obese mice regulates hematopoietic stem cell differentiation

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Obesity is a worldwide epidemic that has many downstream health effects, including musculoskeletal diseases such as arthritis and bone disease. It is not yet fully understood what the mechanisms are that lead to these conditions however it is believed that changes in the function of immune cells in the body may lead to these effects. The microbiome of obese individuals may also impact immune cell function.

Scientists recently published a study looking at the impact that diet and obesity had on the hematopoietic stem cell (HSC) system. They induced a short term obesity as a result of diet in mice. They found that a high fat diet (HFD) altered the bone microenvironment and as a result the HSC niche. The HSC niche which is made up of cells of the osteoblastic lineage that give rise to bone-forming cells seemed to be altered as a result of Gram-positive bacteria in the microbiome.

These changes to the HSC system in the bone marrow as a result of microbiome have important implications for understanding obesity induced bone disease. Altering microbiome composition, and specifically by low-fat diet, may be a possible therapeutic modality for treating bone disease and other immune diseases impacted by the hematopoietic stem cell niche. 

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Regulatory T cells help tolerate commensal bacteria on the skin during first few weeks of life

The human skin is the body’s first line of defense against pathogens that your body comes in contact with. Just like the gut and mouth, the skin lives in communion with bacteria. One important unanswered question that many scientists have is why commensal bacteria do not trigger an inflammatory immune response when they come in contact with the skin. An article published by Cell Press explores exactly this question, looking specifically at regulatory T cells (treg, a type of white blood cell that plays a major role in establishing homeostasis of the immune system).

Researchers engineered the genes of Staphylococcus epidermidis to produce a specific protein antigen that can be fluorescently viewed. To test whether the immune system plays a role in tolerance of skin commensal bacteria the researchers colonized the skin of 6-week-old mice with this fluorescent protein. Three weeks later the mice were compared to a group of control mice and it was found that pre-colonization with the protein was not enough to establish immune tolerance of the bacterial antigens. 

The researchers were curious as to what affect this bacterial antigen on the skin of infant mice had, so the same experiment was done with 7-day-old mice. After 3-4 weeks, when the mice were adult, a significantly diminished immune response to the commensal bacteria could be seen. This shows that exposure during the neonatal period promotes tolerance to commensal bacteria.

After examining adult vs. neonatal skin, this study concludes that there is a difference between the two in terms of immune response and windows of tolerance build-up. Specifically, the period of neonatal skin development seems to be essential in mice for the immune tolerance of commensal bacteria. The implications of this study are important for understanding of the human immune system and bacteria tolerance. Because the skin is our body’s first defense system, it is important to have an understanding as to what mediates its immune response.           

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Microbiome affects blood glucose levels after eating, can help predict glycemic response to foods

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Postprandial (post-meal) glycemic response (PPGR) is the effect that food has on blood glucose levels.   Eating a sugary candy, for example, will raise blood glucose levels, whereas drinking water will not.  PPGR remains an important predictor for metabolic syndrome and type II diabetes, so it has an important role the obesity epidemic.  Unfortunately, PPGR is difficult to predict, and efforts that are based on individual foods themselves have failed.  New research shows that there are many factors, including the microbiome, that are important to predicting blood glucose after a meal.  The research out of Israel and published in the journal Cell presents a new model that can more accurately predict PPGR that is based on personalized factors.

The researchers catalogued 800 peoples’ meals over 7 days while continuously measuring their blood glucose levels.  In addition they monitored their gut microbiota, weight, sleep, and various other lifestyle factors.  After evaluating the data, the scientists realized that identical foods had vastly different PPGRs.  For example, bread could have a 8 fold variation in glycemic response depending on the individual.  In order to explain these differences, the scientists identified several significant associations between the microbiome and the PPGR from specific foods.  For example, on the phyla level high abundances of Proteobacteria and Enterobacteriaceae were associated with poor glycemic controls.  On the species level Eubacterium rectale, which is known to ferment fiber, was correlated with low glycemic response, and Parabacteroides distasonis, which had previously been associated with obesity, was correlated with hight glycemic response.  The scientists then aggregated all of their data, including microbiome data, and created a predictive algorithm for the PPGR from foods for individuals.  This algorithm accurately predicted the glycemic response from foods on a personalized level, and was more informative than general food based predictions.

This study speaks to the power of personalized medicine that is based on the microbiome.  Knowledge of our own microbiome could be used to advise our dietary choices in order to choose foods that will lead to low PPGR, and decrease our risk for metabolic syndrome.  Overall, the scientists determined that of all foods, eating fiber was most beneficial because it lowers glycemic response over the long term.

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Helminths may influence fecundity rates in women

We’ve often discussed helminths and their impact on human health, and researchers have recently provided more insight as to how these infective parasites can influence female reproductive health.  The immune system plays an important role in fecundity in women.  Shifts in immune responses in regulation are dynamic and these changes can have influence on pregnancy.  Helminths are known to induce marked immunological changes and they infect 500 to 800 million people worldwide.  In addition to modulating systemic immune responses, helminths are also known to directly infect reproductive organs or even the fetus.  While studied extensively in animal models, there is little known as to how helminths influence reproductive processes in humans.  A conglomerate group of scientists sought investigate how helminth infection could affect fecundity rates in women, hypothesizing that helminth infection during pregnancy may increase fecundity because the helminth-mediated immunologic responses may in fact modulate those that impair fertility. 

The researchers collected 9 years-worth of health data from 986 Bolivian women who were forager-horticulturists residing in the Amazonian lowlands of the country.  Western medicine and contraceptives are not used in this region, and it is estimated that different types of helminths infect up to 70% of the population.  Cox proportional hazards model first determined that there was an association between helminth infection and birth spacing.  Next, it was shown that women infected with hookworm were associated with a delayed age of first pregnancy.  Interestingly, and in contrast to hookworm, roundworm infection was associated with early first births (in comparison to hookworm) and shortened interbirth intervals.  The researchers postulated that these differences in associations could be explained by each respective helminth species unique effect on the immune system modulation.  Specifically, roundworm infection is associated with regulatory T cell (Treg) Type 2 immune activation, while hookworm infections are associated with mixed Treg immune activation (e.g. both Type 1 and Type 2 activation).  The association with the specific immune response could also explain why roundworm association was shown to be more favorable to conception, as Treg Type 2 activation more closely resembles pregnancy immune system activity while a Type1/Type2 mix more closely resembles an inflammatory response. 

From a broad viewpoint, these findings are interesting as they point to a species-host interaction that may have an underlying - and underappreciated - influence on demographic/population distribution.  The study of helminths is deserving of more attention, as we continue to acquire a wealth of information from their interactions with humans and implications on human health.  

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Antibiotics affect the mouth and gut differently

When we discuss antibiotic resistance, it’s not always clear where the resistance is developing or how exactly the resistance develops. A study out of the UK and Sweden looked at two niches, the gut and the mouth, to understand the difference between how the different parts of the body react to antibiotics.

The scientists discovered that these two parts of the body reacted and recovered very differently after a one-week course of antibiotics. They took fecal and saliva samples prior to the antibiotic regime and then gave the study participants a weeklong course of clindamycin, ciprofloxacin, minocycline, amoxicillin, or a placebo and continued taking fecal and saliva samples for a year.

They found that the oral microbiome recovered much faster than the gut microbiome back to its normal state. It took much longer for the gut microbiome to recover and for participants taking ciprofloxacin, diversity was changed even after 12 months. They also found that while participants largely had genes associated with antibiotic resistance in their gut prior to the trial, the amount of antibiotic resistant genes increased after taking the antibiotic. Antibiotic resistant genes in the mouth remained largely stable before and after treatment.  It was also observed that butyrate production, a health associated short-chain fatty acid, was severely affected by ciprofloxacin and clindamycin.

This raises a number of questions like why does the oral microbiome recover so much faster than the gut microbiome? And why isn’t there a similar increase in antibiotic resistant genes in the mouth like we see in the gut? While this study raises many questions, it provides an opportunity to look at the mouth and better understand what is unique about that environment in comparison to the gut. 

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.