Landmark study reveals link between gut microbes, diet and illnesses

Diets rich in healthy and plant-based foods encourages the presence of gut microbes that are linked to a lower risk of common illnesses, including heart disease, research has found.

A large-scale international study using metagenomics and blood chemical profiling has uncovered a panel of 15 gut microbes associated with lower risks of common conditions such as obesity and type 2 diabetes. The study has been published in Nature Medicine from researchers at King's College London, Massachusetts General Hospital (MGH), Harvard T.H. Chan School of Public Health, the University of Trento, Italy, and health start-up company ZOE.

The PREDICT 1 (Personalized Responses to Dietary Composition Trial 1) analysed detailed data on the composition of participants' gut microbiomes, their dietary habits, and cardiometabolic blood biomarkers. It uncovered strong links between a person's diet, the microbes in their gut (microbiome) and their health.

Researchers identified microbes that positively or negatively correlate 'good' and 'bad' with an individual's risk of certain serious conditions such as diabetes, heart disease and obesity. Surprisingly, the microbiome has a greater association to these markers than other factors, such as genetics. Some of the identified microbes are so novel that they have not yet been named.

The researchers defined a ‘healthy’ diet as one that contained a mix of foods associated with a lower risk of chronic disease. They found that trial subjects who ate such a diet, or one rich in plants, were more likely to have high levels of specific 'good' gut microbes which are associated with a low risk of common illnesses. The researchers also found microbiome-based biomarkers of obesity as well as markers for cardiovascular disease and impaired glucose tolerance, which are key risk factors for COVID. These findings can be used to help create personalised eating plans designed specifically to improve one's health.

Dr Sarah Berry, Reader in Nutrition Sciences at King's College London, said: "As a nutritional scientist, finding novel microbes that are linked to specific foods, as well as metabolic health, is exciting. Given the highly personalised composition of each individuals' microbiome, our research suggests that we may be able to modify our gut microbiome to optimise our health by choosing the best foods for our unique biology."

For example, the findings reveal that having a microbiome rich in Prevotella copri and Blastocystis species was associated with maintaining a favourable blood sugar level after a meal. Other species were linked to lower post-meal levels of blood fats and markers of inflammation.

Nicola Segata PhD, professor and principal investigator of the Computational Metagenomics Lab at the University of Trento, Italy, and leader of the microbiome analysis in the study, said: "We were surprised to see such large, clear groups of what we informally call 'good' and 'bad' microbes emerging from our analysis. It is also exciting to see that microbiologists know so little about many of these microbes that they are not even named yet. This is now a big area of focus for us, as we believe they may open new insights in the future into how we could use the gut microbiome as a modifiable target to improve human metabolism and health."

PREDICT is the largest in-depth nutritional study in the world. PREDICT 1 was an international collaboration to study links between diet, the microbiome, and biomarkers of cardiometabolic health. The researchers gathered microbiome sequence data, detailed long-term dietary information, and results of hundreds of cardiometabolic blood markers from just over 1,100 participants in the U.S. and the U.K. PREDICT 2 completed its primary investigations in 2020 with a further 1,000 U.S participants, and PREDICT 3 launched a few months ago.

Make-up of gut microbiome may influence COVID-19 severity and immune response

The variety and volume of bacteria in the gut, known as the microbiome, may influence the severity of COVID-19 as well as the magnitude of the immune system response to the infection, suggests research published online in the journal Gut.

Imbalances in the make-up of the microbiome may also be implicated in persisting inflammatory symptoms, dubbed ‘long COVID’, the findings suggest. COVID-19 is primarily a respiratory illness, but the evidence suggests that the gut may also have a role.

As the gut is the largest immunological organ in the body and its resident microbes are known to influence immune responses, the researchers wanted to find out if the gut microbiome might also affect the immune system response to COVID-19 infection. They therefore obtained blood and stool samples and medical records from 100 hospital in-patients with laboratory-confirmed COVID-19 infection between February and May 2020 and from 78 people without COVID-19 who were taking part in a microbiome study before the pandemic.

The severity of COVID-19 was classified as mild in the absence of x-ray evidence of pneumonia; moderate if pneumonia with fever and respiratory tract symptoms were detected; severe if patients found it very difficult to breathe normally; and critical if they needed mechanical ventilation or experienced organ failure requiring intensive care. To characterise the gut microbiome, 41 of the COVID patients provided multiple stool samples while in hospital, 27 of whom provided serial stool samples up to 30 days after clearance of SARS-CoV-2, the virus responsible for COVID-19.

Analysis of all 274 stool samples showed that the make-up of the gut microbiome differed significantly between patients with and without COVID-19, irrespective of whether they had been treated with drugs, including antibiotics.

COVID patients had higher numbers of Ruminococcus gnavus, Ruminococcus torques and Bacteroides dorei species than people without the infection.

And they had far fewer of the species that can influence immune system response, such as Bifidobacterium adolescentis, Faecalibacterium prausnitzii and Eubacterium rectale. Lower numbers of F. prausnitzii and Bifidobacterium bifidum were particularly associated with infection severity after taking account of antibiotic use and patient age. And the numbers of these bacteria remained low in the samples collected up to 30 days after infected patients had cleared the virus from their bodies.

COVID-19 infection prompts the immune system to produce inflammatory cytokines in response. In some cases, this response can be excessive (‘cytokine storm’), causing widespread tissue damage, septic shock, and multiorgan failure.

Analysis of the blood samples showed that the microbial imbalance found in the COVID patients was also associated with raised levels of inflammatory cytokines and blood markers of tissue damage, such as C-reactive protein and certain enzymes.

This suggests that the gut microbiome might influence the immune system response to COVID-19 infection and potentially affect disease severity and outcome, say the researchers.

“In light of reports that a subset of recovered patients with COVID-19 experience persistent symptoms, such as fatigue, dyspnoea [breathlessness] and joint pains, some over 80 days after initial onset of symptoms, we posit that the dysbiotic gut microbiome could contribute to immune-related health problems post-COVID-19,” they write.

This is an observational study, and as such, can’t establish cause, added to which the gut microbiome varies widely among different populations, so the changes observed in this study may not be applicable to other COVID patients elsewhere, caution the researchers. But they point to mounting evidence showing that gut microbes are linked to inflammatory diseases within and beyond the gut.

And they conclude: “Bolstering of beneficial gut species depleted in COVID-19 could serve as a novel avenue to mitigate severe disease, underscoring the importance of managing patients’ gut microbiota during and after COVID-19.”

Drinking milk while breastfeeding may reduce the child's food allergy risk

Children of mothers who drink relatively more cows’ milk during breastfeeding are at reduced risk of developing food allergies. That is the conclusion of researchers from Chalmers University of Technology, Sweden, in a new study published in the scientific journal Nutrients.

The result is based on a survey of more than 500 Swedish women's eating habits and the prevalence of allergies in their children at one year of age.

"We have found that mothers of healthy one-year-olds consumed more cows' milk during breastfeeding than mothers of allergic one-year-olds. Though the association is clear, we do not claim that drinking cow's milk would be a general cure for food allergies," says Mia Stråvik, doctoral student in the Division of Food Science at Chalmers University of Technology, and first author of the study.

There are many factors behind the risk of food allergy, not least genetic predisposition. Yet, as Mia Stråvik explains: "Diet is a factor where parents themselves can have direct influence. It is quite common nowadays for young women to avoid drinking milk, due in part to prevailing trends and concerns, some of which are linked to myths about diet."

She points out that allergy to milk protein is uncommon in adults, so most women can consume milk and dairy products themselves without issue. Lactose intolerance is something completely different, when the body cannot break down milk sugars.

The hygiene hypothesis

According to Professor Ann-Sofie Sandberg, Mia Stråvik's supervisor, one possible explanation may be that the milk in the mother's diet contains substances that stimulate the maturity of the immune system.

"In a child's early development, there is a time window where stimulation of the immune system is necessary for the child to develop tolerance to different foods," said Professor Ann-Sofie Sandberg

According to something known as the hygiene hypothesis, early contact with various microorganisms can function as something of a kickstart' for a child's immune system, she explains.

"But, with the lower prevalence of microorganisms nowadays in our more hygienic society, substances taken in through the mother's diet can be another way to stimulate the maturity of the immune system."

Mia Stråvik's study is not the first to link cows’ milk in a mother's diet to a reduced risk of allergies in children. Previous studies, however, have often been based solely on questionnaire responses – both in terms of eating habits and the presence of allergies. In this study both data and conclusions are significantly more robust.

"In this study, we were able to actually verify the women's reported intake of milk and milk products through biomarkers in her blood and breast milk. The biomarkers are two fatty acids formed in the cow's stomach, which are specific to dairy products," said Mia Stråvik. "Furthermore, all the cases of allergy in children were diagnosed by a doctor specialising in child allergies."

The study is part of a more extensive research project built around a family cohort study of 655 families who gave birth at Sunderby Hospital near Luleå, northern Sweden, during the years 2015-2018. The project was initiated, and the cohort established, by Ann-Sofie Sandberg from Chalmers, Professor Agnes Wold at the University of Gothenburg and the chief physician and paediatric allergist Anna Sandin, affiliated with Umeå University and Sunderby Hospital.

The current study is the first scientific publication, focusing mainly on allergies based on data collected from the families in northern Sweden.

A clear connection

The mothers in the study, more than 500, gave detailed accounts of their eating habits on three occasions – in the 34th week of the pregnancy, one month after the birth and four months after birth. At one year of age, the children were medically examined, and all cases of food allergy, atopic eczema and asthma were identified.

After the material was adjusted for various other factors, such as hereditary predisposition or reverse causation, the researchers were able to establish that there was indeed a clear connection between the mother's intake of milk and dairy products and the smaller incidence of food allergy in their children.

"No matter how we looked at and interpreted the data, we came to the same conclusion," states Chalmers researcher and co-author Malin Barman, Assistant Supervisor to Mia Stråvik. "The mechanisms behind why milk has this preventative effect against allergies, however, are still unclear." A further explanation of various hypotheses can be found below.

Another result in the study that Mia Stråvik highlights is that children of breastfeeding mothers, who at the four-month measurement were eating a lot of fruit and berries, tended to suffer from eczema to a much greater extent – though she stresses that further studies are needed before anything can be said with certainty about this connection.

A follow-up study is currently underway to examine the children's health at the age of four.