Tag: gut microbiota

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

Taurine Boosts Microbiotic Defences in the Gut

A new study has discovered that taurine has a role in triggering the gut’s microbiota to identify and destroy invading bacteria, such as Klebsiella pneumoniae, a bacteria commonly found in the gut and responsible for a variety of infections.

It is already known that gut microbiota can protect against infection, but it is not well understood how they accomplish this. A better of understanding of how they confer protection will aid the development of replacements for current antibiotic drugs, which currently harm gut microbiota and whose effectiveness is waning.

Taurine is a complementary (non-essential amino acid, involved in helping break down fats and is present in bile acid. Most taurine is produced by the body but some is also required in the diet. Certain seafoods, seaweed, poultry and beef are good sources of taurine.

The scientists believed that the taurine helped prevent against bacterial colonisation by producing hydrogen sulphide, but during their research they also discovered that a single infection was sufficient to prepare the gut microbiota to resist a second infection. The liver and gallbladder which produce and store bile acids, can develop long-term protection against infection.

While investigating further, the researchers discovered a particular type of bacteria, Deltaproteobacteria, which protected the gut against colonisation by infectious bacteria and which was activated by taurine. Taurine fed to mice in drinking water helped to shield against infection by boosting the function of the protective bacteria, but those fed bismuth subsalicylate (a common over-the-counter diarrhoea treatment), the infection protection diminished, because bismuth suppresses hydrogen sulphide production in the gut.

Source: News-Medical.Net

Faecal Transplants Safe in the Long Term for C. Diff Treatment

A new study from the Mayo Clinic has provided more evidence for the safety and efficacy of faecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI).

Recruiting 609 patients diagnosed with CDI, 20% of whom were overweight or obese and 22.8% had inflammatory bowel disease (IBD), FMT was performed with a stool product from a common donor. At a short term follow-up, >60% of patients had diarrhoea, <33% had constipation, and 9.5% reported additional CDI episodes after one year. At long-term follow up (median 3.7 years), there 73 new diagnoses out of 477 patients, 13% had gastrointestinal problems, 10% had weight gain, and 11.8% had new unrelated infections.

However, this was marked by the appearance of additional medical conditions such as weight gain and irritable bowel syndrome, which the authors indicated should be investigated further. The study also did not use a standardised questionnaire for IBS, making those results harder to generalise, and there was no control group. However, administering questionnaires over an extended period to all participants instead of only a brief period shortly after FMT explains why there are fewer symptoms reported compared to other studies.  

A separate study with 207 patients receiving FMT showed 143 new diagnoses after the procedure, with a mean follow-up of 34 months. The researchers conducting this second study attribute the ability of FMT to reduce CDI to enhancements in CD4+ T cell and antibody-mediated immunity to C. difficile toxins such as TcdB.

“These results are important for the design of disease monitoring strategies and highlight that future study of how FMT influences pathogen specific immunity is warranted: specifically, determining if effectively restoring the TcdB specific cellular repertoire to healthy control proportions contributes to treatment success of FMT,” the researchers wrote.

These studies add to the growing body of evidence that show FMT combined with antibiotics is an effective way to treat CDI.

Source: MedPage Today

Journal information (first source): Saha S, et al. Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection, Gastroenterol 2021; DOI: 10.1053/j.gastro.2021.01.010. 

Journal information (second source): Cook L, et al. Fecal microbiota transplant treatment for recurrent Clostridioides difficile infection enhances adaptive immunity to TcdB, Gastroenterol 2021; DOI: 10.1101/2020.06.05.20114876.

Healthy Country Childhood: The Protective “Farm Effect” on Asthma

The presence of a diverse gut microbiome appears to exert a protective effect against asthma, which may explain the largely protective “farm effect” on asthma.

European researchers analysed faecal samples from over 700 infants raised on farms, and found a strong environmental effect. It was anticipated that nutrition would be a strong contributor to gut microbiome maturation, but there were unanticipated environmental effects such as exposure to animal sheds.

Researchers found that faecal butyrate (related to butyrate, a short-chain fatty acid), which is already known to protect against asthma in mice, had an inverse association with asthma. They ascribed this to gut bacteria such as Roseburia and Coprococcus which have the potential of producing short chain fatty acids. Children with more matured gut microbiomes had Roseburia and Coprococcus present.

“Our study provides further evidence that the gut may have an influence on the health of the lung. A mature gut microbiome with a high level of short chain fatty acids had a protective effect on the respiratory health of the children in this study. This suggests the idea of a relevant gut-lung axis in humans,” said Dr. Markus Ege, professor for clinical-respiratory epidemiology at the Dr. von Hauner Children’s Hospital. “This also means, however, that an immature gut microbiome may contribute to the development of diseases. This emphasizes the need for prevention strategies in the first year of life, when the gut microbiome is highly plastic and amenable to modification.”

Source: News-Medical.Net

Gut Microbiota Have Large Effects on Immune System

For the first time, immune cells in the bloodstream have been shown to be affected by the makeup of gut microbiota.

In recent years, there has been increased interest in gut microorganisms and their influence on human health, partly as a result of improvements in the ability to study them. Much prior understanding of gut microbiota on the immune system comes from animal studies; this study was able to examine the effects in humans. This study used data from allogeneic stem cell and bone marrow transplants (BMTs), where the patient’s blood formation system is destroyed by radiation or chemotherapy and replaced with stem cells from a donor’s bone marrow. The patient is given antibiotics until the transplanted cells are able to re-establish the immune system, the gut microbiota being destroyed in the process and then re-establishing once the antibiotics are withdrawn. Over a period of ten years, a multidisciplinary team with the Memorial Sloan Kettering Cancer Center took blood and faecal samples from BMT patients.

Study author Dr Joao Xavier said, “Our study shows that we can learn a lot from stool—biological samples that literally would be flushed down the toilet. The result of collecting them is that we have a unique dataset with thousands of datapoints that we can use to ask questions about the dynamics of this relationship.”
“The parallel recoveries of the immune system and the microbiota, both of which are damaged and then restored, gives us a unique opportunity to analyse the associations between these two systems,” lead author Dr Jonas Schluter said.

A higher diversity of microbiota was shown to lower the risk of death following a BMT, and a lower diversity increased the risk of graft-versus-host disease, a potentially fatal condition where the transplanted marrow attacks the host’s body.

“Because experiments with people are often impossible, we are left with what we can observe,” Dr. Schluter noted. “But because we have so many data collected over a period of time when the immune system of patients as well as the microbiome shift dramatically, we can start to see patterns. This gives us a good start toward understanding the forces that the microbiota exerts on the rebuilding of the immune system.”

Source: Medical Xpress

Journal information: Jonas Schluter et al. The gut microbiota is associated with immune cell dynamics in humans, Nature (2020). DOI: 10.1038/s41586-020-2971-8

Gut Microbiome is Linked to Pulmonary Disease

A link has been shown between the gut microbiome and chronic obstructive pulmonary disease (COPD), a lung disease with an often poor prognosis.

Senior author Prof Phil Hansbro, Director of the Centenary University of Technology Sydney Centre for Inflammation, said, “It’s already known that the lung microbiome is a contributing factor in COPD. We wanted to see if the gut environment was also somehow involved–to determine whether the gut could act as a reliable indicator of COPD or if it was connected in some way to the development of the disease.”

Stool samples of COPD patients showed elevated levels of the bacteria Streptococcus and Lachnospiraceae. Additionally a unique metabolite signature was identified in individuals with COPD, created by the chemical by-products of the metabolic process.

First author Dr Kate Bowerman from the University of Queensland said, “Our research indicates that the gut of COPD patients is notably different from healthy individuals. This suggests that stool sampling and analysis could be used to non-invasively diagnose and monitor for COPD,” she said.
“The ‘gut-lung axis’ describes the common immune system of the lung and gastrointestinal tract. This means that activity in the gut can impact activity in the lung. Our COPD findings suggest that the gut microbiome should now also be considered when looking for new therapeutic targets to help treat lung disease,” Prof Hansbro said.

Source: Medical Xpress