Tag: gut microbiota

Categories : Neurology PaediatricsTags :

Autism and ADHD are Linked to Gut Flora Disturbance in First Year of Life

On By ModernMedia
Photo by Christian Bowen on Unsplash

Disturbed gut flora during the first years of life is associated with diagnoses such as autism and ADHD later in life. One explanation for this disturbance could be from antibiotic treatment. This is according to a study led by researchers at the University of Florida and Linköping University and published in the journal Cell.

The study is the first prospective study to examine gut flora composition and a large variety of other factors in infants, in relation to the development of the children’s nervous system. The researchers have found many biological markers that seem to be associated with future neurological development disorders, such as autism spectrum disorder, ADHD, communication disorder and intellectual disability.

“The remarkable aspect of the work is that these biomarkers are found at birth in cord blood or in the child’s stool at one year of age over a decade prior to the diagnosis,” says Eric W Triplett, professor at the Department of Microbiology and Cell Science at the University of Florida, USA, one of the study leaders.

Antibiotic treatment could be involved

The study is part of the ABIS (All Babies in Southeast Sweden) study led by Johnny Ludvigsson at Linköping University. More than 16 000 children born in 1997–1999, representing the general population, have been followed from birth into their twenties. Of these, 1197 children (7.3%), have been diagnosed with autism spectrum disorder, ADHD, communication disorder or intellectual disability. Many lifestyle and environmental factors have been identified through surveys conducted on several occasions during the children’s upbringing. For some of the children, the researchers have analysed substances in umbilical cord blood and bacteria in their stool at the age of one.

“We can see in the study that there are clear differences in the intestinal flora already during the first year of life between those who develop autism or ADHD and those who don’t. We’ve found associations with some factors that affect gut bacteria, such as antibiotic treatment during the child’s first year, which is linked to an increased risk of these diseases,” says Johnny Ludvigsson, senior professor at the Department of Biomedical and Clinical Sciences at Linköping University, who led the study together with Eric W. Triplett.

Children who had repeated ear infections before one year of age had a higher risk of a developmental neurological disorder diagnosis later in life. It is probably not the infection itself that is the culprit, but the researchers suspect a link to antibiotic treatment. They found that the presence of Citrobacter bacteria or the absence of Coprococcus bacteria increased the risk of future diagnosis. One possible explanation may be that antibiotic treatment has disturbed the composition of the gut flora in a way that contributes to neurodevelopmental disorders. The risk of antibiotic treatment damaging the gut flora and increasing the risk of diseases linked to the immune system, such as type 1 diabetes and childhood rheumatism, has been shown in previous studies.

“Coprococcus and Akkermansia muciniphila have potential protective effects. These bacteria were correlated with important substances in the stool, such as vitamin B and precursors to neurotransmitters which play vital roles orchestrating signalling in the brain. Overall, we saw deficits in these bacteria in children who later received a developmental neurological diagnosis,” says study first author Angelica Ahrens, Assistant Scientist in Eric Triplett’s research group at the University of Florida.

The present study also confirms that the risk of developmental neurological diagnosis in the child increases if the parents smoke. Conversely, breastfeeding has a protective effect, according to the study.

Differences at birth

In cord blood taken at the birth of children, the researchers measured substances such as fatty acids and amino acids, as well as exogenous ones such as nicotine and environmental toxins. They compared substances in the umbilical cord blood of 27 children diagnosed with autism with the same number of children without a diagnosis.

It turned out that children who were later diagnosed had low levels of several important fats in the umbilical cord blood. One of these was linolenic acid, which is needed for the formation of omega 3 fatty acids with anti-inflammatory properties and other effects in the brain. The same group also had higher levels than the control group of a PFAS substance, used as flame retardants and shown to negatively affect the immune system in several different ways. PFAS substances can enter the body via drinking water, food and the air we breathe.

Opens up new possibilities

As the relationships found in the Swedish children may not be generalisable to other populations, studies in other populations are needed. Another question is whether gut flora imbalance is a triggering factor or whether it has occurred as a result of underlying factors, such as diet or antibiotics. Yet even accounting for risk factors that might affect the gut flora, they found that the link between future diagnosis remained for many of the bacteria.

The research is at an early stage and more studies are needed, but the discovery that many biomarkers for future developmental neurological disorders can be observed at an early age opens up the possibility of developing screening protocols and preventive measures in the long term.

Source: Linköping University

Categories : Cancer GastrointestinalTags :

Bacteria Subtype Linked to Growth in up to 50% of Human Colorectal Cancers

On By ModernMedia
Human colon cancer cells. Credit: National Cancer Institute

Researchers at Fred Hutchinson Cancer Center have found that a specific subtype of a microbe commonly found in the mouth is able to travel to the gut and grow within colorectal cancer tumours. This microbe is also a culprit for driving cancer progression and leads to poorer patient outcomes after cancer treatment.

The findings, published in Nature, could help improve therapeutic approaches and early screening methods for colorectal cancer, which is the second most common cause of cancer deaths in adults in the U.S. according to the American Cancer Society.

Examining colorectal cancer tumours removed from 200 patients, the Fred Hutch team measured levels of Fusobacterium nucleatum, a bacterium known to infect tumours. In about 50% of the cases, they found that only a specific subtype of the bacterium was elevated in the tumour tissue compared to healthy tissue.

The researchers also found this microbe in higher numbers within stool samples of colorectal cancer patients compared with stool samples from healthy people.

“We’ve consistently seen that patients with colorectal tumours containing Fusobacterium nucleatum have poor survival and poorer prognosis compared with patients without the microbe,” explained Susan Bullman, PhD, Fred Hutch cancer microbiome researcher and co-corresponding study author. “Now we’re finding that a specific subtype of this microbe is responsible for tumour growth. It suggests therapeutics and screening that target this subgroup within the microbiota would help people who are at a higher risk for more aggressive colorectal cancer.”

In the study, Bullman and co-corresponding author Christopher D. Johnston, PhD, Fred Hutch molecular microbiologist, along with the study’s first author Martha Zepeda-Rivera, PhD, a Washington Research Foundation Fellow and Staff Scientist in the Johnston Lab, wanted to discover how the microbe moves from its typical environment of the mouth to a distant site in the lower gut and how it contributes to cancer growth.

First they found a surprise that could be important for future treatments. The predominant group of Fusobacterium nucleatum in colorectal cancer tumours, thought to be a single subspecies, is actually composed of two distinct lineages known as “clades.”

“This discovery was similar to stumbling upon the Rosetta Stone in terms of genetics,” Johnston explained. “We have bacterial strains that are so phylogenetically close that we thought of them as the same thing, but now we see an enormous difference between their relative abundance in tumours versus the oral cavity.”

By separating out the genetic differences between these clades, the researchers found that the tumour-infiltrating Fna C2 type had acquired distinct genetic traits suggesting it could travel from the mouth through the stomach, withstand stomach acid and then grow in the lower gastrointestinal tract. The analysis revealed 195 genetic differences between the clades.

Then, comparing tumour tissue with healthy tissue from patients with colorectal cancer, the researchers found that only the subtype Fna C2 is significantly enriched in colorectal tumour tissue and is responsible for colorectal cancer growth.

Further molecular analyses of two patient cohorts, including over 200 colorectal tumours, revealed the presence of this Fna C2 lineage in approximately 50% of cases.

The researchers also found in hundreds of stool samples from people with and without colorectal cancer that Fna C2 levels were consistently higher in colorectal cancer.

“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Johnston said.

Source: Fred Hutchinson Cancer Center

Categories : Cardiovascular Disease GastrointestinalTags :

Certain Gut Bacteria Linked to Reduced Cardiovascular Disease Risk

On By ModernMedia
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

Changes in the gut microbiome have been implicated in a range of diseases including type 2 diabetes, obesity, and inflammatory bowel disease. Now, a team of researchers has found that microbes in the gut may affect cardiovascular disease as well. In a study published in Cell, the team has identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.

Researchers at the Broad Institute of MIT and Harvard along with Massachusetts General Hospital analysed metabolites and microbial genomes from more than 1400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for cardiovascular disease.

The team discovered that bacteria called Oscillibacter take up and metabolise cholesterol from their surroundings, and that people carrying higher levels of the microbe in their gut had lower levels of cholesterol. They also identified the mechanism the bacteria likely use to break down cholesterol. The results suggest that interventions that manipulate the microbiome in specific ways could one day help decrease cholesterol in people. The findings also lay the groundwork for more targeted investigations of how changes to the microbiome affect health and disease.

“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier, who is a core institute member and a professor at Harvard Medical School and Massachusetts General Hospital.

Postdoctoral researcher Chenhao Li and research scientist Martin Stražar, both in Xavier’s lab, were co-first authors on the study.

Cholesterol cues

In the past decade, other researchers have uncovered links between composition of the gut microbiome and elements of cardiovascular disease, such as a person’s triglycerides and blood sugar levels after a meal. But scientists haven’t been able to target those connections with therapies in part because they lack a complete understanding of metabolic pathways in the gut.

In the new study, the Broad team gained a more complete and detailed picture of the impact of gut microbes on metabolism. They combined shotgun metagenomic sequencing, which profiles all of the microbial DNA in a sample, with metabolomics, which measures the levels of hundreds of known and thousands of unknown metabolites. They used these tools to study stool samples from the Framingham Heart Study.

“The project outcomes underline the importance of high-quality, curated patient data,” Stražar said. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”

More than 16 000 associations between microbes and metabolic traits were found, one of them particularly strong: People with several species of bacteria from the Oscillibacter genus had lower cholesterol levels than those who lacked the bacteria. The researchers found that species in the Oscillibacter genus were surprisingly abundant in the gut, representing on average 1 in every 100 bacteria.

The researchers then wanted to figure out the biochemical pathway the microbes use to break down cholesterol. To do this, they first needed to grow the organism in the lab. Fortunately, the lab has spent years collecting bacteria from stool samples to create a unique library that also included Oscillibacter.

After successfully growing the bacteria, the team used mass spectrometry to identify the most likely byproducts of cholesterol metabolism in the bacteria. This allowed them to determine the pathways the bacteria uses to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that can then be broken down by other bacteria and excreted from the body. Next, the team used machine-learning models to identify the candidate enzymes responsible for this biochemical conversion, and then detected those enzymes and cholesterol breakdown products specifically in certain Oscillibacter in the lab.

The team found another gut bacterial species, Eubacterium coprostanoligenes, that also contributes to decreased cholesterol levels. This species carries a gene that the scientists had previously shown is involved in cholesterol metabolism. In the new work, the team discovered that Eubacterium might have a synergistic effect with Oscillibacter on cholesterol levels, which suggests that new experiments that study combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.

Microbial messages

The human gut microbiome remains mostly unmapped, but the team believes they have paved the way for the discovery of other similar metabolic pathways impacted by gut microbes, which could be targeted therapeutically.

“There are many clinical studies trying to do faecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” Li said. “Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”

“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions,” Li added. “Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host.”

Source: Broad Institute of MIT and Harvard

Categories : Gastrointestinal Obstetrics & GynaecologyTags :

Metabolic Diseases may be Driven by Gut Microbiome, Loss of Ovarian Hormones

On By ModernMedia
Photo by Ravi Patel on Unsplash

The gut microbiome interacts with the loss of female sex hormones to exacerbate metabolic disease, including weight gain, fat in the liver and the expression of genes linked with inflammation, researchers report in the journal Gut Microbes.

The findings, using rodent models, may shed light on why women are at significantly greater risk of metabolic diseases such as obesity and Type 2 diabetes after menopause, when ovarian production of female sex hormones diminishes.

“Collectively, the findings demonstrate that removal of the ovaries and female hormones led to increased permeability and inflammation of the gut and metabolic organs, and the high-fat diet exacerbated these conditions,” said Kelly S. Swanson, the director of the Division of Nutritional Sciences and a professor in nutrition at the University of Illinois Urbana-Champaign who is a corresponding author of the paper. “The results indicated that the gut microbiome responds to changes in female hormones and worsens metabolic dysfunction.”

“This is the first time it has been shown that the response of microbiome to the loss of ovarian hormone production can increase metabolic dysfunction,” said first author Tzu-Wen L. Cross, a professor of nutrition science and the director of the Gnotobiotic Animal Facility at Purdue University. Cross was a doctoral student at the U. of I. when she began the research.

“The gut microbiome is sensitive to sex hormone changes and can further impact the risk of disease development.”

Cross said early microbiome research, beginning around 2005, looked at how the microbiome contributes to obesity development, but most of those studies focused on males.

“Metabolic dysfunction that is driven by the loss of ovarian-function in menopausal women – and how much the gut microbiome contributes to that – has not been studied. The aetiology is clearly very complex, but those gut-microbiome related factors are certainly components that we speculated play a role,” she said.

The scientists created diet-induced obesity in female mice and simulated the loss of female sex hormones by removing the ovaries in half of the population to examine any metabolic and inflammatory changes, including those to enzymes in the gut. The diets for both groups of mice were identical except for the proportion of fat, which constituted 60% or 10% of calories for those in the high-fat and low-fat groups, respectively.

In the second leg of the study, faecal samples were harvested from mice with or without ovaries and implanted in germ-free mice to study the impact on weight gain and metabolic and inflammatory activity in the gut, liver and fat tissue.

“The mice that were recipients of the gut microbiome of ovariectomized mice gained more weight and fat mass, and they had greater expression of genes in the liver associated with inflammation, obesity, Type 2 diabetes, fatty liver disease and atherosclerosis compared with those in the control group,” Swanson said.

Assessing the severity of fatty tissue and triglyceride concentrations in the liver, the scientists found that the triglyceride levels were significantly higher and fatty deposits in the liver and groin were greater in the mice that consumed the high-fat diet compared with all other treatment groups.

Those on the high-fat diet and those without ovaries had significantly larger fat cells, which are associated with cell death and the infiltration of macrophages. Along with elevated expression of the genes associated with inflammation and macrophage markers, these mice had lower expression of genes that are involved with glucose and lipid metabolism.

In the donor mice without ovaries that consumed the low-fat diet, the scientists found increased levels of beta-glucuronidase, an enzyme produced by the colon and some intestinal bacteria that breaks down and recycles steroidal metabolites such as oestrogen and various toxins, including carcinogens.

The scientists also examined the expression of genes coding for tight-junction proteins, which affect cell membranes’ permeability. They found that the mice without ovaries and those fed the high-fat diet had lower levels of these proteins in the liver and colon, which suggested their gut barriers were more permeable, compromised by either their diet or the absence of female hormones.

In the livers of the recipient mice that received transplants from donors without ovaries, the scientists found elevated expression levels of the gene for arginase-1, which plays a critical role in the elimination of nitrogenous waste. High levels of this protein have been associated with cardiovascular problems such as hypertension and atherosclerosis.

Source: University of Illinois at Urbana-Champaign, News Bureau

Categories : Gastrointestinal Respiratory DiseasesTags :

Gut Microbiome Composition Affects Sensitivity to Respiratory Viruses

On By ModernMedia
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

The composition of microbiota found in the gut influences how susceptible mice are to respiratory virus infections and the severity of these infections, according to Georgia State University researchers. The findings, published in the journal Cell Host & Microbe, report that segmented filamentous bacteria, a bacterial species found in the intestines, protected mice against influenza virus infection when these bacteria were either naturally acquired or administered.

This protection against infection also applied to respiratory syncytial virus (RSV) and severe acute SARS-CoV-2. To maintain this protection, the study noted that segmented filamentous bacteria required immune cells in the lungs called basally resident alveolar macrophages.

In this study, the researchers investigated how differences in specific microbial species can impact outcomes of respiratory virus infections and how they might do so, which hasn’t been well defined previously.

They studied mice with discrete microbiome differences and mice differing in only the presence or absence of segmented filamentous bacteria.

Viral titers in the lung were measured several days after infection and varied significantly depending on the nature of the microbiome of the different animal groups.

“These findings uncover complex interactions that mechanistically link the intestinal microbiota with the functionality of basally resident alveolar macrophages and severity of respiratory virus infection,” said Dr. Andrew Gewirtz, co-senior author of the study and Regents’ Professor in the Institute for Biomedical Sciences at Georgia State.

The study found that in segmented filamentous bacteria-negative mice, basally resident alveolar macrophages were quickly depleted as respiratory virus infection progressed.

However, in segmented filamentous bacteria-colonised mice, basally resident alveolar macrophages were altered to resist influenza virus infection depletion and inflammatory signaling.

The basally resident alveolar macrophages disabled influenza virus, in large part by activating a component of the immune system referred to as the complement system.

“We find it remarkable that the presence of a single common commensal bacterial species, amidst the thousands of different microbial species that inhabit the mouse gut, had such strong impacts in respiratory virus infection models and that such impacts were largely attributable to reprogramming of basally resident alveolar macrophages,” said D. Richard Plemper, co-senior author of the study, Regents’ Professor and director of the Center for Translational Antiviral Research at Georgia State.

“If applicable to human infections, these findings will have major implications for the future risk assessment of a patient to advance to severe disease.”

“We find it highly unlikely that segmented filamentous bacteria is the only gut microbe capable of impacting the phenotype of alveolar macrophages, and consequently, proneness to respiratory virus infection,” Gewirtz said.

“Rather, we hypothesize that gut microbiota composition broadly influences proneness to respiratory virus infection. Microbiota mediated programming of basally resident alveolar macrophages may not only influence the severity of acute respiratory virus infection, but may also be a long-term post-respiratory virus infection health determinant.”

Source: Georgia State University

Categories : Diet and Nutrition Immune SystemTags :

Yet Another Impact of High-fat Diets: Immune Changes

On By ModernMedia
Photo by Patrick Fore on Unsplash

A new study from UC Riverside has added more reasons to stick to New Year’s diet resolutions: it showed that that high-fat diets affect genes linked not only to obesity, colon cancer and irritable bowels, but also to the immune system, brain function, and potentially COVID risk.

While other studies have examined the effects of a high-fat diet, this one is unusual in its scope. UCR researchers fed mice three different diets over the course of 24 weeks where at least 40% of the calories came from fat. Then, they looked not only at the microbiome, but also at genetic changes in all four parts of the intestines.

One group of mice ate a diet based on saturated fat from coconut oil, another got a monounsaturated, modified soybean oil, a third got an unmodified soybean oil high in polyunsaturated fat. Compared to a low-fat control diet, all three groups experienced concerning changes in gene expression, the process that turns genetic information into a functional product, such as a protein.

Plant-based or not, high-fat is bad

“Word on the street is that plant-based diets are better for you, and in many cases that’s true. However, a diet high in fat, even from a plant, is one case where it’s just not true,” said Frances Sladek, a UCR cell biology professor and senior author of the new study.

The study, published in Scientific Reports, documents the many impacts of high-fat diets. Some of the intestinal changes did not surprise the researchers, such as major changes in genes related to fat metabolism and the composition of gut bacteria. For example, they observed an increase in pathogenic E. coli and a suppression of Bacteroides, which helps protect the body against pathogens.

Other observations were more surprising, such as changes in genes regulating susceptibility to infectious diseases. “We saw pattern recognition genes, ones that recognise infectious bacteria, take a hit. We saw cytokine signalling genes take a hit, which help the body control inflammation,” Sladek said. ‘So, it’s a double whammy. These diets impair immune system genes in the host, and they also create an environment in which harmful gut bacteria can thrive.”

The team’s previous work with soybean oil documents its link to obesity and diabetes, both major risk factors for COVID. This paper now shows that all three high-fat diets increase the expression of ACE2 and other host proteins that are used by COVID spike proteins to enter the body.

Additionally, the team observed that high-fat food increased signs of stem cells in the colon. “You’d think that would be a good thing, but actually they can be precursors to cancer,” Sladek said.

In terms of effects on gene expression, coconut oil showed the greatest number of changes, followed by the unmodified soybean oil. Differences between the two soybean oils suggest that polyunsaturated fatty acids in unmodified soybean oil, primarily linoleic acid, play a role in altering gene expression.

Negative changes to the microbiome in this study were more pronounced in mice fed the soybean oil diet. This was unsurprising, as the same research team previously documented other negative health effects of high soybean oil consumption.

Soybeans are fine, but watch the oil

In 2015, the team found that soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in mice. In 2020, the researchers team demonstrated the oil could also affect genes in the brain related to conditions like autism, Alzheimer’s disease, anxiety, and depression.

Interestingly, in their current work they also found the expression of several neurotransmitter genes were changed by the high fat diets, reinforcing the notion of a gut-brain axis that can be impacted by diet.

The researchers have noted that these findings only apply to soybean oil, and not to other soy products, tofu, or soybeans themselves. “There are some really good things about soybeans. But too much of that oil is just not good for you,” said UCR microbiologist Poonamjot Deol, who was co-first author of the current study along with UCR postdoctoral researcher Jose Martinez-Lomeli.

Also, the studies were conducted using mice, and mouse studies do not always translate to the same results in humans. However, humans and mice share 97.5% of their working DNA. Therefore, the findings are concerning, as soybean oil is the most commonly consumed oil in the United States, and is increasingly being used in other countries, including Brazil, China, and India.

By some estimates, Americans tend to get nearly 40% of their calories from fat, which mirrors what the mice were fed in this study. “Some fat is necessary in the diet, perhaps 10 to 15%. Most people though, at least in this country, are getting at least three times the amount that they need,” Deol said.

Readers should not panic about a single meal. It is the long-term high-fat habit that caused the observed changes. Recall that the mice were fed these diets for 24 weeks. “In human terms, that is like starting from childhood and continuing until middle age. One night of indulgence is not what these mice ate. It’s more like a lifetime of the food,” Deol said.

That said, the researchers hope the study will cause people to closely examine their eating habits.

Source: University of California – Riverside

Categories : Cardiovascular DiseaseTags :

Researchers ID Two Probiotics that can Help Bring Down Hypertension

On By ModernMedia

Recent studies suggest that probiotics may offer a protective effect against hypertension, but how gut microbiota can regulate blood pressure has remained something of a mystery. Now a study published in mSystems showed that two probiotics, Bifidobacterium lactis and Lactobacillus rhamnosus, returned blood pressure in hypertensive mouse models to normal levels. The researchers also tracked how those probiotics altered the animals’ gut microbial mix over 16 weeks, identifying specific microbes and metabolic pathways that may help explain the protective effect. 

“Accumulated evidence supports an antihypertensive effect of probiotics and probiotic fermented foods in both in vitro and in vivo experiments,” said computational biologist Jun Li, PhD, at the City University of Hong Kong. Her team worked with that of microbiologist Zhihong Sun, PhD, at Inner Mongolia Agricultural University, on the study. “So, we believed that the dietary intake of probiotic foods would well supplement traditional hypertension treatment.” 

Previous studies have connected the rising rates of hypertension worldwide to increasing consumption of sugar. It likely boosts blood pressure through many mechanisms, such as increased insulin resistance or salt retention, but in recent years researchers have also investigated sugar’s effect on the gut microbiome. 

In the new study, the researchers tested the two probiotic strains on mice that developed hypertension after consuming water mixed with fructose. Over the course of 16 weeks, they measured the animals’ blood pressures every 4 weeks. They found that fructose-fed mice that received either probiotic showed significantly lower blood pressures than those fed a high fructose diet and not treated with probiotics. 

In addition, the researchers found no difference between the blood pressure readings of fructose-fed mice that received probiotics and a control group of mice that only drank water. According to Li, that suggests probiotic interventions would maintain blood pressure at normal levels. 

The researchers used shotgun metagenomic sequencing to probe connections between the altered gut microbiota and the change in blood pressure. They found that a high-fructose diet in the mice led to an increase in Bacteroidetes and a decrease in Firmicutes bacteria; however, treatment with probiotics returned those populations to those found in the control group. In addition, the analysis identified new microbial signatures associated with blood pressure: Increased levels of Lawsonia and Pyrolobus bacteria, and reduced levels of Alistipes and Alloprevotella, were associated with lower blood pressure. 

The researchers are now planning a large clinical trial to see if the protective effect of probiotics extend to people with hypertension. “Probiotics present a promising avenue in preventive medicine,” Sun said, “offering potential in regulating hypertension and reshaping our approach to cardiovascular health.”

Source: American Society for Microbiology

Categories : Allergies Immune SystemTags :

Does the ‘Hygiene Hypothesis’ Still Hold Water?

On By ModernMedia
Photo by Andrea Piacquadio on Unsplash

Over the last few decades, there has been growing popularity for the ‘hygiene hypothesis’, which suggests that some level of microbial exposure helps protects against developing allergy. Now, an article published in Science Immunology by researchers from Karolinska Institutet challenges this hypothesis by showing that mice with high infectious exposures from birth have the same, if not an even greater ability to develop allergic immune responses than ‘clean’ laboratory mice.

Studies have suggested that certain infections might reduce the production of inflammatory antibodies to allergens and alter the behaviour of T cells involved in allergies. It has also been suggested that ‘good’ intestinal bacteria could shut off inflammation elsewhere in the body.

Robust allergic responses

Researchers have now compared the allergic immune response in ‘dirty’ wildling mice to those of typical clean laboratory mice. They found very little evidence that the antibody response was altered or that the function of T cells changed in a meaningful way. Nor did anti-inflammatory responses evoked by good gut bacteria appear to be capable of switching off the allergic immune response. On the contrary, wildling mice developed robust signs of pathological inflammation and allergic responses when exposed to allergens.

“This was a little unexpected but suggests that it’s not as simple as saying, ‘dirty lifestyles will stop allergies while clean lifestyles may set them off’. There are probably very specific contexts where this is true, but it is perhaps not a general rule,” says Jonathan Coquet, co-author of the study and Associate Professor at Karolinska Institutet.

More like the human immune system

The wildling mice are genetically identical to clean laboratory mice but are housed under ‘semi-natural’ conditions and have rich microbial exposures from birth.

“The immune systems of wildling mice better represent the human immune system and so we hope that they can bring us closer to the truth of how microbes act upon the body,” says Jonathan Coquet.

The findings contribute to the general understanding of how allergies may arise and may also have clinical implications. Using experimental infections to treat patients suffering from inflammatory diseases has also been attempted in recent clinical trials. For example, infecting people with worms or performing faecal transplantations has been proposed as a tool to combat inflammatory diseases. Newborns delivered through C-section, have had maternal faecal transplantation and bacterial supplementation with the aim of promoting good bacteria in the baby’s gut and the child’s future health.

Beneficial effects of exposure not clear as we’d like

“This field of research can provide important insights into how infections and microbes can be used to facilitate health, but it is still in its infancy. Our study is a reminder that general and broad exposures to microbes may not have the clear beneficial effects that we wish them to have,” says Susanne Nylén, co-author of the study and Associate Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

Source:

Categories : GastrointestinalTags :

Silent but Violent: Taurine-consuming Bacteria Protects the Gut with Toxic Gas

On By ModernMedia
Photo by Pablo Stanic on Unsplash

Researchers have discovered a new intestinal bacterim that feeds exclusively on taurine and produces the foul-smelling gas hydrogen sulfide. The results, currently published in Nature Communications, show that Taurinivorans muris protects against Klebsiella and Salmonella, two important pathogens.

Chemical warfare in the gut

One of the ways the gut microbiome helps regulated health is in contributing to the levels of hydrogen sulfide – the toxic gas responsible for foul-smelling farts. Having small amounts of hydrogen sulfide in the gut is a good thing; in fact, it’s essential for a number of physiological processes, and can even protect against pathogens. Hydrogen sulfide-producing microbes in the gut may help “choke out” oxygen-dependent pathogens such as Klebsiella, making it harder for them to colonise. However, excessive levels can have negative consequences and have been associated with gut inflammation and damage to the intestinal lining.

Taurine plays yet another a role

The bacterium Bilophila wadsworthia is one of the most important taurine utilizers in humans. In the current study, researchers led by Alexander Loy at CeMESS, the Centre for Microbiology and Environmental Systems Science of the University of Vienna, have discovered a new genus of hydrogen sulfide-producing bacteria in the mouse intestine. “The bacterium we described has a rather unbalanced diet,” explains Loy, “it specialises in consuming taurine.” Taurine is a semi-essential amino acid, synthesised in small amounts in the liver but mostly obtained through the diet – especially meat, dairy and seafood. 

Like hydrogen sulfide, taurine is implicated in a plethora of physiological processes. Recent studies have found a link between taurine and healthy ageing – it seems this nutrient may stave away age-related disease. In light of these findings, the discovery of a new gut microbe that feeds exclusively on taurine (aptly named Taurinivorans muris) is another piece of an exciting puzzle. “By isolating the first taurine degrader in the mouse gut, we’re one step closer to understanding how these gut microbes mediate animal and human health” explains Huimin Ye, lead author of the study. 

To access sufficient taurine in the gut, however, Taurinivorans muris needs the help of other gut microbes to release it from bile acids. Taurine-containing bile acids are produced in the liver and are increasingly released into the intestine during a high-fat diet to help our body digest fats. The activities of the bacteria in the intestine in turn influence the bile acid metabolism in the liver. The results of the Viennese researchers therefore also contribute to a better understanding of these complex interactions in bile acid metabolism, which has an impact on processes and diseases throughout the body.

Taurine-degrading microbes choke out pathogens

One of the most important functions of the symbiotic microbes in the gut is to defend against pathogens. The microbiome has a versatile arsenal of protective mechanisms – and utilising taurine to create hydrogen sulfide is one of them. “Hydrogen sulfide may suppress the oxygen-dependent metabolism of some pathogens,” explains Ye. In the present study, the researchers found that Taurinivorans muris has a protective role against Klebsiella and Salmonella, two important gut pathogens. “The protective mechanism of Taurinivorans muris against pathogens may be via hydrogen sulfide but is essentially not yet fully understood” adds Alexander Loy. Taurine is one of the most important sources of hydrogen sulfide production in the gut. The study thus generates basic knowledge on the physiological interactions between the different gut microbes and their hosts, which is necessary to develop new microbiome-based therapies.

Source: EurekAlert!

Categories : Allergies PaediatricsTags :

Common Gut Microbiota Link to the Development of Childhood Allergies

On By ModernMedia
Photo by Andrea Piacquadio on Unsplash

Several major childhood allergies may all stem from the gut microbiome gut, according to a new study published in Nature Communications. The research identifies gut microbiome features and early life influences that are associated with children developing any of four common allergies. The study, led by researchers at the University of British Columbia and BC Children’s Hospital, could lead to methods of predicting whether a child will develop allergies, and methods to prevent their development.

“We’re seeing more and more children and families seeking help at the emergency department due to allergies,” said Dr Stuart Turvey, paediatrics professor at UBC and co-senior author on the study, noting that as many as one in three children in Canada have allergies.

The study is one of the first to examine four distinct school-aged paediatric allergies at once: atopic dermatitis, asthma, food allergy and allergic rhinitis. While these allergic diseases each have unique symptoms, the Turvey lab was curious whether they might have a common origin linked to the infant gut microbiota composition.

“These are technically different diagnoses, each with their own list of symptoms, so most researchers tend to study them individually,” says Dr Charisse Petersen, co-senior author on the paper and postdoctoral fellow in the Turvey lab. “But when you look at what is going wrong at a cellular level, they actually have a lot in common.”

For the study, researchers examined clinical assessments from 1115 children who were tracked from birth to age five. Roughly half of the children (523) had no evidence of allergies at any time, while more than half (592) were diagnosed with one or more allergic disorders by an expert physician. The researchers evaluated the children’s microbiomes from stool samples collected at clinical visits at three months and one year of age.

The stool samples revealed a bacterial signature that was associated with the children developing any of the four allergies by five years of age. The bacterial signature is a hallmark of dysbiosis, or an imbalanced gut microbiota, that likely resulted in a compromised intestinal lining and an elevated inflammatory response within the gut.

“Typically, our bodies tolerate the millions of bacteria living in our guts because they do so many good things for our health. Some of the ways we tolerate them are by keeping a strong barrier between them and our immune cells and by limiting inflammatory signals that would call those immune cells into action,” says Courtney Hoskinson, a PhD candidate at UBC and first author on the paper. “We found a common breakdown in these mechanisms in babies prior to the development of allergies.”

Many factors can shape the infant gut microbiota, including diet, place and delivery method of birth and antibiotics exposure. The researchers examined how these types of influences affected the balance of gut microbiota and the development of allergies.

“There are a lot of potential insights from this robust analysis,” says Dr Turvey. “From these data we can see that factors such as antibiotic usage in the first year of life are more likely to result in later allergic disorders, while breastfeeding for the first six months is protective. This was universal to all the allergic disorders we studied.”

Now the researchers hope to leverage the findings to inform treatments that correct an imbalanced gut microbiota and could potentially prevent allergies from developing.

“Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime,” says Dr Turvey.

Source: University of British Columbia