Tag: gut microbiota

IBS Dietary Therapy Works Best with Certain Gut Microbiomes

Beneficial gut bacteria. Credit: Darryl Leja, National Human Genome Research Institute, National Institutes of Health

People who respond well to the irritable bowel syndrome (IBS) dietary therapy of reduced fermentable carbs have an abundance of particular types of bacteria in their gut, reveals research published online in the journal Gut.

The composition of the gut microbiome is thought to have a major role in the development of IBS. Restricting fermentable carbs, found in many foods including wheat, onions, and milk, is usually recommended to ease symptoms, an approach known as the low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet. But why this diet works is not fully understood.

In a bid to fill this knowledge gap, the researchers analysed stool samples of 56 people with IBS and 56 people who lived with them, but without the condition, to identify the microbial profile and genes involved in converting food into active molecules while on their usual diet.

They then assessed the clinical response in 41 of these pairs after 4 weeks on the low FODMAP diet by reviewing their stool samples again.

Before adoption of the low FODMAP diet, analysis of the stool samples of those with IBS revealed two distinct microbial ‘signatures’, which the researchers referred to as ‘pathogenic-like’ (IBSP) and as ‘health-like’ (IBSH).

The pathogenic microbial signature was abundant in harmful Firmicutes sp, including known disease causing bacteria, such as C. difficileC. sordellii and C. perfringens, but very low in beneficial Bacteroidetes species.

The lactic acid bacteria Streptococcus parasanguinis and Streptococcus timonensis that are usually found in the mouth were also abundant. And bacterial genes for amino acid and carbohydrate metabolism were overexpressed, which may explain the excess of some metabolites that are linked to IBS symptoms, say the researchers.

The healthy microbial signature of the other IBS patients was similar to that found in the comparison group (household members).

After 4 weeks on the low FODMAP diet, the microbiome of the comparison group and those with the healthy microbial profile stayed the same.

But the microbiome of those with the pathogenic profile became healthier, with an increase in Bacteroidetes, and a fall in Firmicutes species. And the bacterial genes involved in the metabolism of amino acids and carbs were no longer overexpressed.

In 3 out of 4 of IBS patients, symptoms improved. But the clinical response to the low FODMAP diet was greater in those with IBS and a pathogenic microbial signature than it was in those with IBS and a healthy microbial signature in their gut.

“The evidence associating diet, the microbiome and symptoms in [pathogenic IBS] is compelling, but studies following the introduction of candidate organisms into an animal model are needed to prove the relationship is causal,”  the researchers cautioned.

Nevertheless, they suggest their findings could lead to a microbial signature to identify those who would respond best to a low FODMAP diet and better manage those who wouldn’t.

“If the bacteria represented in the [pathogenic] subtype are shown to play a pathogenic role in IBS, perhaps through their metabolic activity, this provides a target for new therapies and an intermediate [marker] by which to assess them,” they suggest.

In a linked editorial, Professor Peter Gibson and Dr Emma Halmos of Melbourne’s Monash University, describe the introduction and adoption of the FODMAP diet as “a major change in the management of patients with irritable bowel syndrome (IBS) towards integrated care.

But while “an effective symptomatic therapy, [it’s] one that carries risks associated with exacerbating disordered eating, challenging nutritional adequacy and putatively inducing dysbiotic gut microbiota,” they added.

They point out some limitations of the research, including that FODMAP intake was poorly assessed, fibre intake,which can also influence the microbiome wasn’t reported and patient drop-out reduced the power of the study.

Nevertheless, the authors concluded that “the beauty of [the study] is not in its definitive nature, but that it enables the creation of feasible innovative hypotheses that can be examined by focused studies. Perhaps the FODMAP diet is not just a symptomatic therapy.” 

Source: BMJ

Gut Microbes and Antibiotics Impact Inflammatory Pain

C difficile. Source: CDC

A study in rats showed that gut microbiomes and antibiotic use could modulate inflammatory pain.

Published in The Journal of Pain, the study examined the impact of antibiotics on the gut microbiome and how antibiotic use can alter inflammatory pain in subjects with or without access to exercise.

According to Glenn Stevenson, Ph.D., professor of psychology within the School of Social and Behavioral Sciences, this is the first publication to assess how antibiotic-induced changes to the gut microbiome impact inflammatory pain distal to the gut (in the limbs, for example).

The study determined the effects of vancomycin on inflammatory pain-stimulated and pain-depressed behaviours in rats, which was induced with formalin. Oral vancomycin administered in drinking water attenuated pain-stimulated behaviour, and prevented formalin pain-depressed wheel running. Faecal microbiota transplantation produced a non-significant trend toward reversal of vancomycin’s effect on pain-stimulated behaviour. Vancomycin depleted Firmicutes and Bacteroidetes gut populations while partially sparing Lactobacillus species and Clostridiales. The vancomycin treatment effect was associated with an altered profile in amino acid concentrations in the gut.

The results indicate that manipulation of the gut microbiome may be one method to attenuate inflammatory pain amplitude. Additionally, results indicated that the antibiotic-induced shift in gut amino acid concentrations may be a causal mechanism for this reduction in pain.

The research for this study took four years to complete, Prof Stevenson said, adding that the link between amino acids and pain reduction is “highly novel.”

Source: University of New England

A Cognitive Rejuvenating Effect with Gut Microbe Transplant

Source: Pixabay

A novel approach to reverse aspects of ageing-related deterioration in the brain and cognitive function via the microbes in the gut was revealed in research published in Nature Aging.

With ageing populations increasing worldwide, a key challenge is the development of strategies to maintain healthy brain function. This ground-breaking research with gut microbes lays open new possibilities such as microbial-based interventions to slow down brain ageing and cognitive problems associated with it.

The work was carried out by researchers at Microbiome Ireland (APC) at University College Cork (UCC).

There is a growing appreciation of the importance of the microbes in the gut on all aspects of physiology and medicine. In this most recent study, the authors demonstrated that by transplanting gastrointestinal microbes from young into old mice, they were able to rejuvenate aspects of brain and immune function.

Study leader Professor John F Cryan said: “Previous research published by the APC and other groups internationally has shown that the gut microbiome plays a key role in aging and the ageing process. This new research is a potential game changer, as we have established that the microbiome can be harnessed to reverse age-related brain deterioration. We also see evidence of improved learning ability and cognitive function”.

Despite the promising results, Prof Cryan cautioned that “it is still early days and much more work is needed to see how these findings could be translated in humans”.

APC Director Prof Paul Ross stated that “This research of Prof Cryan and colleagues further demonstrates the importance of the gut microbiome in many aspects of health, and particularly across the brain/gut axis where brain functioning can be positively influenced. The study opens up possibilities in the future to modulate gut microbiota as a therapeutic target to influence brain health”.

Source: University College Cork

Host Genes Can Hinder H. Pylori Eradication

Helicobacter pylori is a strong risk factor for gastric cancer and other gastrointestinal disorders, and efforts to eradicate it using a combination of antibiotics and proton pump inhibitors (PPIs) often fail.

A new study has linked this eradication failure with genetic variations that increase the activity of the CYP2C19 enzyme, which metabolises first-generation PPIs.

These so-called ‘fast metabolisers’ may prevent PPIs from suppressing gastric acid production, which is necessary for successful H. pylori eradication.

Analysing 57 studies from 11 countries, the researchers found that the failure rate of H. pylori eradication more than doubled in people with a version of the CYP2C19 gene that increased its metabolic activity. Their results were published in Gastroenterology.

However, CYP2C19 variants were not linked to eradication failure if the fast metabolisers were treated with newer PPIs such as esomeprazole and rabeprazole, which are less metabolised by the enzyme or which bypass CYP2C19 metabolism.

Further well-designed studies are needed to determine whether eradication rates could be improved with higher or more frequent dosages of first-generation PPIs to people with the fast metaboliser gene variant, noted the paper’s corresponding author, Shailja Shah, MD, MPH.
“Even small improvements in H. pylori eradication rates would likely translate to substantial collateral health, economic and societal benefits,” the researchers concluded.

Source: Vanderbilt University

Centenarians’ Unique Microbiomes Protect Against Bacterial Infections

Source: Miika Luotio on Unsplash

A new study has discovered that people who live to be 100 or older have a unique microbiome that may protect against certain bacterial infections  including those caused by multidrug-resistant bacteria. The findings, published in Nature, could point to new ways to treat chronic inflammation and bacterial disease.

A team of researchers studied microbes from  faecal samples of 160 Japanese centenarians who had an average age of 107. They found that centenarians, compared to people aged 85 to 89 and those between 21 and 55, had higher levels of several bacterial species that produce molecules called secondary bile acids. Secondary bile acids are generated by microbes in the colon and are thought to help protect the intestines from pathogens and regulate the body’s immune responses.

Next, the researchers treated common infection-causing bacteria in the lab with the secondary bile acids that were elevated in the centenarians. One molecule, called isoalloLCA, was found to strongly inhibit the growth of the  antibiotic-resistant bacterium Clostridioides difficile. Feeding mice infected with C. difficile diets supplemented with isoalloLCA similarly suppressed levels of the bacteria. The team also found that isoalloLCA potently inhibited or killed many other gram positive pathogens, suggesting that isoalloLCA may play a role in keeping the delicate equilibrium of microbial communities in a healthy gut.

“The ecological interaction between the host and different processes in bacteria really suggests the potential of these gut bugs for health maintenance,” said Plichta, a computational scientist at the Broad.

Additional studies from different regions around the world with more participants and longer duration could help find a causal link between longevity and bile acids. The bacteria identified in this study could help researchers in the meantime discover how to treat infections caused by antibiotic-resistant bacteria by manipulating bile acid.

“A unique cohort, international collaboration, computational analysis, and experimental microbiology all enabled this discovery that the gut microbiome holds the keys to healthy aging,” said co-first author Xavier, core institute member at the Broad. “Our collaborative work shows that future studies focusing on microbial enzymes and metabolites can potentially help us identify starting points for therapeutics.”

Source: Broad Institute of MIT and Harvard

Journal information: Sato Y, Atarashi K, et al. Unique bile acid-metabolizing bacteria in centenarians’ microbiome. Nature. Online July 29, 2021. DOI:10.1038/s41586-021-03832-5

Common Gut Bacteria Could Inhibit SARS-CoV-2

Bifidobacterium eriksonii, stained with fluorescent antibodies. Source: Public Health Image Library

South Korean researchers have found that certain common gut bacteria produce compounds that inhibit SARS-CoV-2. 

The research was presented on June 20 at World Microbe Forum, an online meeting of the American Society for Microbiology (ASM), the Federation of European Microbiological Societies (FEMS), and several other societies that taking place online June 20-24.

Previous clinical findings had shown that some patients with moderate to severe COVID experience gastrointestinal symptoms, while others show signs of infection in the lungs only.

“We wondered whether gut resident bacteria could protect the intestine from invasion of the virus,” said Mohammed Ali, a PhD student in Medicine at Yonsei University in South Korea.

To investigate this hypothesis, the researchers screened dominant bacteria inhabiting the gut for activity against SARS-CoV-2. Their efforts revealed that Bifidobacteria, already shown to suppress other bacteria such as H. pylori and have proven active against irritable bowel syndrome, had such activity, said Ali. Bifidobacteria are common in the guts of breast fed infants, which is partly driven by the bifidogenic activities of specific mother milk-derived oligosaccharides

The researchers also searched for potential illness-fighting compounds in databases containing microbially produced molecules, and discovered some that might also be useful against SARS-CoV-2. “To train our model we leveraged previous coronavirus datasets in which several compounds were tested against targets from coronaviruses,” explained Ali. “This approach seems to be significant as those targets share features in common with SARS-CoV-2.”

Ali emphasised the ecological nature of his approach to this work, pointing out that numerous existing antibiotics and cancer therapies are themselves compounds that bacteria use to compete with each other within the gastrointestinal tract, and that these were initially purified from microbial secretions.

“Finding microbes that secrete anti-coronavirus molecules will be a promising method to develop natural or engineered probiotics to expand our therapeutics prevention techniques, to provide a more sustainable way to combat the viral infection,” said Ali.

Source: American Society for Microbiology

Beneficial Microbiota can be Restored at Birth in C-section Babies

Photo by Christian Bowen on Unsplash

Babies born by caesarean section lack the same healthy bacteria as those born vaginally, but a Rutgers-led study for the first time finds that these natural bacteria can be restored.

The human microbiota, consisting of trillions of bacteria, viruses, fungi and other microorganisms, live in and on our bodies, some potentially harmful while others provide benefits. During labour and birth, women naturally impart a small group of colonisers to their babies’ sterile bodies, which helps their immune system to develop. But antibiotics and C-sections disrupt this conferring of microbes and are related to increased risks of obesity (59% increase), asthma (21% increase) and metabolic diseases. ‘Vaginal seeding‘, where a baby delivered by C-section is swabbed with their mother’s vaginal fluids at birth, is becoming increasingly popular.

According to the World Health Organization, C-section is needed in about 15 percent of births to avoid risking the life of the mother or child. However, caesarean birth rates continue to rise worldwide with recent (2016) reported rates of 24.5% in Western Europe, 32% in North America, and 41% in South America.

To see how well babies could be seeded with the mother’s microbiota after birth, the researchers followed 177 babies from four countries over the first year of their lives. Of these, 98 were born vaginally and 79 were born by C-section, 30 of which were swabbed with a maternal vaginal gauze right after birth.

Analysis showed that the microbiota of the C-section babies swabbed with their mother’s vaginal fluids was similar to that of vaginally born babies. Also, the mother’s vaginal microbiomes on the day of birth were similar to other areas of their bodies (gut, mouth and skin), indicating that maternal vaginal fluids help to colonise bacteria across their babies’ bodies.

This was the first large observational study to show that ‘vaginal seeding’ normalises the microbiome development during their first year of life. The next step would be conducting randomised clinical trials to determine if the microbiota normalisation translates into disease protection, the researchers said.

“Further research is needed to determine which bacteria protect against obesity, asthma and allergies, diseases with underlying inflammation,” said senior author Maria Gloria Dominguez Bello, a professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. “Our results support the hypothesis that acquiring maternal vaginal microbes normalises microbiome development in the babies.”

Source: University News

A New Bacterium Might Help Treat Type 2 Diabetes and Obesity

E. Coli bacteria. Image by CDC
E. Coli bacteria. Image by CDC

A newly discovered bacterium has been shown to have a possible link to type 2 diabetes and obesity, and may yield pathways to possible treatments.

It began when Patrice Cani, FNRS researcher at University of Louvain (UCLouvain), and his team repeatedly observed that a certain bacterium, Subdoligranulum, is usually lacking in obese and diabetic people, while it is systematically present in healthy people. Based on this, they decided to examine this family of bacteria.

Currently only one cultivated strain of this family is available in the world (the only known member of a large family) and was not the strain that was seen to be decreased in obese and diabetic people. This is not unusual: nearly 70% of bacteria in the intestine have not yet been identified — this is called the dark matter of the intestine.

In 2015, the team then set out to isolate the bacterium themselves in order to learn about its action on the human body, knowing that it is only present in healthy people. To find a second member of the family, the scientists spent two years searching, isolating and cultivating nearly 600 intestinal bacteria. 

All of this was in vain. Instead, the UCLouvain team uncovered a bacterium of a new, previously unknown kind. They named it Dysosmobacter welbionis: Dysosmo (“which smells bad”, in Greek), bacter (bacterium) is the bacterium which stinks, “Because, when you grow it, it has a slight odour,” they explained. Welbionis for WELBIO, the organisation in the Walloon region which funded this research.

The bacterium is peculiar for a number of reasons, including the fact that it produces butyrate. Though many other bacteria produce this colon cancer-promoting molecule, for example by strengthening the intestinal barrier and boost immunity. But the team also discovered that Dysosmobacter welbionis was less present in people with type 2 diabetes.

By analysing the microbiota from 12 000 faecal samples gathered from around the world, the UCLouvain scientists observed that the bacteria is present in 70% of the population. As to why such a widely prevalent bacteria was never discovered before, the answer likely lies in the improved cultivation techniques developed by the UCLouvain team.

The UCLouvain team including doctoral student Emilie Moens de Hase and post-doctoral fellow Tiphaine Le Roy then tested the action of Dysosmobacter welbionis in mice. The Results? The bacteria increased the number of mitochondria (a kind of power plants within cells that burns fat), thereby lowering sugar levels and weight, in addition to having strong anti-inflammatory effects. All these effects are very promising for type 2 diabetic and obese subjects and resemble those of Akkermansia, a beneficial bacterium that is at the heart of the research in Patrice Cani’s lab.

They also observed that the bacteria’s effects are not limited to the gut: Scientists have found that certain molecules produced by Dysosmobacter migrate around the body and have distant actions as well. This could explain the effects the bacteria have on the fat tissues, and also opens the doors for a possible impact on other diseases such as cancer. This is currently being investigated by the team.

The next step is to test the action of Dysosmobacter welbionis coupled with that of Akkermansia, in order to see if their association has cumulative effect on health, while always keeping in mind the fight against type 2 diabetes, inflammatory diseases, obesity and cancer. “That’s the fun of research: you dig for dinosaur bones and you end up finding a treasure,” Patrice Cani enthused.

Source: Université catholique de Louvain

Journal reference: Roy, T. L., et al. (2021) Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut. doi.org/10.1136/GUTJNL-2020-323778.

Diet Affects both Breast Microbiome and Breast Cancer Tumours

Breast cancer cells. Image source: National Cancer Institute on Unsplash

The breast has its own microbiome of bacteria, and new research has shown it can be influenced by diet, as can breast cancer tumours.

In 2018, scientists at Wake Forest School of Medicine, part of Wake Forest Baptist Health, showed that diet, just like the gut microbiome, can influence the breast microbiome.

Now, new research shows that diet, including fish oil supplements, can alter not only the breast microbiome, but also breast cancer tumours. The findings were published online in Cancer Research.

To untangle the relationship between microbiome, diet and cancer risk, researchers undertook a multi-pronged approach to study both animal models and breast cancer patients.

“Obesity, typically associated with a high-fat diet consumption, is a well-known risk factor in postmenopausal breast cancer,” said Katherine L. Cook, PhD, assistant professor in the surgery – hypertension and cancer biology departments at Wake Forest School of Medicine. “But there’s still a lot we don’t know about the obesity link to microbiomes and the impact on breast cancer and patient outcomes.”

In the first part of the study, mice susceptible to breast cancer were fed either a high-fat or a low-fat diet. Mice consuming the high-fat diet had more tumours, which were also larger and more aggressive than the tumours in the low-fat diet group.

Next, to study the microbiome, researchers performed faecal transplants. Mice consuming the low-fat diet received the high-fat diet microbiome transplant, and mice consuming the high-fat diet received the low-fat diet microbiome transplant. Unexpectedly, mice that consumed the low-fat diet and received a high-fat diet microbiome had just as many breast tumours as mice on the high-fat diet.

“Simply replacing the low-fat diet gut microbiome to the microbiome of high-fat diet consuming animals was enough to increase breast cancer risk in our models,” Cook said. “These results highlight the link between the microbiome and breast health.”

Researchers also conducted a double-blind placebo-controlled clinical trial with breast cancer patients, with patients either receiving placebo or fish oil supplements for two to four weeks before lumpectomy or mastectomy.

Results showed that fish oil supplementation significantly modified the breast microbiome in both non-cancerous and malignant breast tissue. For example, scientists found longer-term administration of fish oil supplements (four weeks) increased the proportional abundance of Lactobacillus in the breast tissue near the tumour. Lactobacillus is a genus of bacteria shown to decrease breast cancer tumour growth, suggesting potential anti-cancer properties of this intervention. Researchers also found decreased proportional abundance of Bacteroidales and Ruminococcus microbes in the breast tumours of patients taking the supplements, though the significance of this is not understood.

“This study provides additional evidence that diet plays a critical role in shaping the gut and breast microbiomes,” concluded Dr Cook. “Ultimately, our study highlights that potential dietary interventions might reduce breast cancer risk.”

Dr Cook’s team is also conducting further studies to see if probiotic supplements can affect microbiome populations in mammary glands and in breast tumours.

Source: Wake Forest Baptist Medical Center

Gut Microbiome Changes are Linked to Ageing and Longevity

Ageing in humans is marked by compositional changes in the gut microbiome that become more unique later in life.

Researchers from the Institute for Systems Biology (ISB) analysed gut microbiome, phenotypic and clinical data from over 9000 people across three independent cohorts. Health and survival outcomes were tracked from longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old).

The researchers found that, starting in mid-to-late adulthood, gut microbiomes became increasingly unique as individuals aged, corresponding with a steady decline in the abundance of core bacterial genera common across humans.

Strikingly, while microbiomes became increasingly unique to each individual in healthy aging, the metabolic functions the microbiomes were carrying out shared common traits. Gut microbiome uniqueness was highly correlated with several microbially-derived metabolites in blood plasma. One of them, tryptophan-derived indole, has been shown to extend lifespan in mice. Another metabolite, phenylacetylglutamine, showed the strongest association with uniqueness, and is known to be highly elevated in the blood of people over 100.

“This uniqueness signature can predict patient survival in the latest decades of life,” said study leader Dr Tomasz Wilmanski, who led the study. Healthy individuals aged around 80 showed continued microbial drift toward a uniqueness, but this drift was not seen in less healthy individuals of the same age.

“Interestingly, this uniqueness pattern appears to start in mid-life—40-50 years old—and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age,” Wilmanski said. Indoles are known to reduce inflammation in the gut, for example, and chronic inflammation is believed to drive age-related morbidities.

“Prior results in microbiome-aging research appear inconsistent, with some reports showing a decline in core gut genera in centenarian populations, while others show relative stability of the microbiome up until the onset of aging-related declines in health,” said co-corresponding author, microbiome specialist Dr Sean Gibbons. “Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, we show two distinct aging trajectories: (1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and (2) the maintenance of core microbes in less healthy individuals.”

This analysis highlights the fact that the adult gut microbiome continues to develop with advanced age in healthy individuals, but not in unhealthy ones, and that microbiome compositions associated with health in early-to-mid adulthood may not be compatible with health in late adulthood.

Source: Medical Xpress

Journal information: Gut microbiome pattern reflects healthy ageing and predicts survival in humans, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00348-0