The research findings have been published in the renowned journal Nature Communications: Dual human milk oligosaccharide-fibre utilisation is a selection cue for the weaning gut microbiome.

“We have long known that breastfeeding is important for infants’ health. What is new is that we can now explain how the sugars in breast milk, HMOs, also help to select the bacterial communities associated with a healthy gut microbiota later in life. This underlines the importance of combining breastfeeding with solid baby food at this stage of child’s development,” says Maher Abou Hachem, professor at DTU Bioengineering and senior author of the study.

The study reveals a previously unknown mechanism that gives specific gut bacteria an advantage in the competition to inhabit the infant’s gut during weaning, because they are endowed to metabolise both HMOs from breast milk and fibres from plant-based foods.

The results suggest that the weaning period is a crucial developmental window, during which the combination of breast milk and solid food, promotes the maturation of the gut microbiota to the adult-like community that is maintained during adulthood. On the long term, this new knowledge may contribute to the development of better nutritional solutions for infants and strengthen our understanding of how early nutrition affects health later in life.

“The findings are important in daily clinical practice as an additional justification to the already strong emphasis on promoting the mother’s own milk production and breastfeeding when infants and young children are admitted to a neonatal intensive care unit due to preterm birth or critical illness,” says Consultant Lise Aunsholt from the Department of Intensive Care for Newborns and Young Children at Rigshospitalet.

“It is encouraging to know that when we advise a mother to continue breastfeeding after discharge – and for as long as possible during the transition to solid foods – this will potentially have a positive impact on the child for the rest of their life,” she says.

According to the researchers, the study shows that breast milk not only supports the infant’s nutrition during infancy but also helps to select the bacteria that become a permanent part of the gut microbiota later in life.

Close collaboration between DTU and TUH

The study was carried out in close collaboration between researchers from DTU and clinical research environments at the Technical University Hospital (TUH – see fact box)

The researchers analysed the changes in bacteria and their genes over the weaning phase. This gave them insight into which bacteria were present and what the bacteria were doing. At the same time, the researcherscultured the bacteria in the laboratory under conditions resembling the environment in the human gut. In this way, they were able to identify the bacteria capable of metabolising both HMOs from breast milk and dietary fibres from solid food.

“The collaboration between DTU’s technological and biological expertise and the clinical environments at TUH has been crucial in enabling us to link knowledge about the bacteria’s functions to the development of the gut microbiota in children. This provides unique insight into how early dietary choices affect health later in life,” says Maher Abou Hachem.

Could pave the way for new nutritional solutions

The researchers believe that this new knowledge sets the stage for the development of future nutritional solutions for infants and targeted interventions that support the establishment of healthy gut bacterial community.

The results also suggest that the weaning period may be a crucial time for preventive measures against diseases that are later in life associated with disturbances in the gut microbiota.

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In a study published in Gut Microbes Reports, researchers at Tulane University School of Medicine found that subjects following a Mediterranean diet developed distinctly different gut bacteria patterns compared to those eating a typical Western diet. These bacterial changes correlated with better memory and cognitive performance.

“We’ve known that what we eat affects brain function, but this study explores how that could be happening,” said lead author Rebecca Solch-Ottaiano, PhD, neurology research instructor at Tulane’s Clinical Neuroscience Research Center. “Our findings suggest that dietary choices can influence cognitive performance by reshaping the gut microbiome.”

The study found that rats fed a Mediterranean-style diet rich in olive oil, fish and fiber over 14 weeks showed increases in four beneficial types of gut bacteria and decreases in five others compared to rats eating a Western diet high in saturated fats. These bacterial changes were linked to improved performance on maze challenges designed to test memory and learning.

Specifically, higher levels of bacteria such as Candidatus Saccharimonas were associated with better cognitive performance, while increased levels of other bacteria, such as Bifidobacterium, correlated with poorer memory function.

The Mediterranean diet group also showed better cognitive flexibility — the ability to adapt to new information — and improved working memory compared to the Western diet group. They maintained lower levels of “bad” LDL cholesterol.

This study is the first to assess the effects of the Mediterranean on microbiota and cognitive function outcomes relative to the Western diet in a rodent model. The researchers used young rats approximately equivalent in age to 18-year-old humans to model the effects of diet during a critical developmental period. The diets were based on human consumption and used ingredients reflecting the complexity of human diets. The Mediterranean diet (MeDi) showed clear benefits for cognitive flexibility, memory, and gut health, suggesting potential parallels in young adults whose brains and bodies are still maturing.

“Our findings suggest that the Mediterranean diet or its biological effects could be harnessed to improve scholastic performance in adolescents, or work performance in young adults,” said corresponding author Dr. Demetrius M. Maraganore, Herbert J. Harvey, Jr. Chair of Neurosciences. “While these findings are based on animal models, they echo human studies linking the Mediterranean diet to improved memory and reduced dementia risk.”

The researchers emphasize that larger human studies are needed to confirm these effects and better understand the complex relationship between diet, gut bacteria, and brain function in young people.

For those interested in following a Mediterranean eating pattern, key components include:
– Olive oil as the primary fat source
– Abundant vegetables, fruits and whole grains
– Fish and lean proteins
– Limited red meat and saturated fats
– High fiber intake from various plant sources

Other Tulane co-authors of the study include Elizabeth B. Engler-Chiurazzi, Colin Harper, Savannah Wasson, Sharon Ogbonna, Blake Ouvrier, Hanyun Wang, Madison Prats, Katherine McDonald, Ifechukwude J. Biose, Lori A. Rowe, MaryJane Jones, Chad Steele and Gregory Bix.

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The human gut microbiome is a collection of trillions of microorganisms that live inside the intestinal tract. The bacteria there can affect nearly all systems of the body, including metabolism and the building and maintaining of the immune system.

“Research has shown that people who have a lot of different microbes have better health, and a better diet, than those who don’t have much bacterial diversity,” said Penny M. Kris-Etherton, Evan Pugh University Professor of Nutritional Sciences, Penn State.

For the peanut study, which published in the journal Clinical Nutrition, Kris-Etherton and her colleagues compared the effects of snacking on 28 grams (approx. 1 ounce) of peanuts per day, versus a higher carbohydrate snack—crackers and cheese. At the end of six weeks, participants who ate the peanut snack showed an increased abundance of Ruminococcaceae, a group of bacteria linked to healthy liver metabolism and immune function.

In the herbs and spices study, which published in The Journal of Nutrition, scientists analyzed the impact of adding blends of herbs and spices — such as cinnamon, ginger, cumin, turmeric, rosemary, oregano, basil and thyme — to the controlled diets of participants at risk for cardiovascular disease. The team examined three doses — about 1/8 teaspoon per day, a little more than 3/4 teaspoon per day and about 1 1/2 teaspoon per day. At the end of four weeks, participants showed an increase in gut bacteria diversity, including an increase in Ruminococcaceae, most notably with the medium and high doses of herbs and spices.

“It’s such a simple thing that people can do,” said Kris-Etherton. “The average American diet is far from ideal, so I think everyone could benefit by adding herbs and spices. It’s also a way of decreasing sodium in your diet but flavoring foods in a way that makes them palatable and, in fact, delicious! Taste is really a top criterion for why people choose the foods they do.”

In both studies, the increase in Ruminococcaceae and bacterial diversity was viewed positively, as scientists continue to learn more about the connection between the gut microbiota and a spectrum of health factors, from blood pressure to weight. However, Kris-Etherton is quick to point out that more research is needed to understand all of the implications.

She said, “We need a lot more research on the microbiome to see what its proper place is in terms of overall health.”

Other authors on the papers are as follows:

Peanut study: Philip A. Sapp, Penn State Department of Nutrition Sciences; Elke A. Arnesen, Jeremy R. Chen See and Regina Lamendella, Juniata College Department of Biology and Wright Labs; and Kristina S. Petersen, Penn State Department of Nutrition Sciences and Texas Tech University Department of Nutritional Sciences.

The work was supported by The Peanut Institute and Penn State’s Clinical & Translational Research Institute. This research was also supported by a grant to Juniata College from the Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program, as well as by the National Science Foundation.

Herbs and Spices study: Kristina S. Peterson, Penn State Department of Nutrition Sciences and Texas Tech University Department of Nutritional Sciences; Samantha Anderson, Jeremy R. Chen See, Jillian Leister and Regina Lamendella, Juniata College Department of Biology and Wright Labs.

This study was funded by the McCormick Science Institute. In addition, the study was supported by the National Center for Advancing Translational Sciences, NIH. The study also received support for computational resources from the Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program, as well as the National Science Foundation.

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A substance produced by gut microorganisms can lead to scarring and blood vessel damage in patients with scleroderma, a new study suggests.

The intestinal microbiome regulates immunity, and its alterations play a role in autoimmune conditions such as scleroderma. However, until now, researchers did not know how alterations in the intestinal microbiome contribute to fibrosis and vascular damage characteristic of scleroderma.

Researchers from Michigan Medicine investigated how a compound generated by the gut microbiome called trimethylamine N-oxide, or TMAO, could cause changes to cellular processes in scleroderma that trigger fibrosis, inflammation and vascular injury.

TMAO is formed in the liver after the gut metabolizes nutrients such as choline and carnitine, which are abundant in the Western diet that is rich in meat. Results published in iScience reveal that the TMAO can reprogram cells to become scar-forming myofibroblasts, which lead to fibrosis and vascular damage. Moreover, the enzyme responsible for the formation of TMAO, called FMO3, is elevated in patients with scleroderma.

“We have uncovered a novel mechanism linking the Western diet, the gut microbiome and some of the devastating effects of scleroderma,” said John Varga, M.D., senior author of the paper and chief of the Division of Rheumatology at University of Michigan Health. “We will next examine whether drugs, or food products like virgin olive oil, can be used to block formation of this compound in the gut to treat fibrosis.”

The research team also included investigators from the Cleveland Clinic and Northwestern University.

Journal Reference:

1. Seok-Jo Kim, Swarna Bale, Priyanka Verma, Qianqian Wan, Feiyang Ma, Johann E. Gudjonsson, Stanley L. Hazen, Paul W. Harms, Pei-Suen Tsou, Dinesh Khanna, Lam C. Tsoi, Nilaksh Gupta, Karen J. Ho, John Varga. Gut microbe-derived metabolite trimethylamine N-oxide activates PERK to drive fibrogenic mesenchymal differentiation. iScience, 2022; 25 (7): 104669 DOI: 10.1016/j.isci.2022.104669

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University of Vienna

Extremely premature infants are at a high risk for brain damage. Researchers have now found possible targets for the early treatment of such damage outside the brain: Bacteria in the gut of premature infants may play a key role. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies.

Complex interplay: the gut-immune-brain axis

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. “We investigated the role this axis plays in the brain development of extreme preterm infants,” says the first author of the study, David Seki. “The microorganisms of the gut microbiome — which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes — are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain,” explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage

“In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury,” adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. “Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided.”

Comprehensive study of the development of extremely premature infants

Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. “Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage,” explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. “We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process,” he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods — the team examined the microbiome using 16S rRNA gene sequencing, among other methods — the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants’ brains.

Research continues with two studies

The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. “How the children’s motoric and cognitive skills develop only becomes apparent over several years,” explains Angelika Berger. “We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. ” The most important cooperation partners for the project are already on board: “The children’s parents have supported us in the study with great interest and openness,” says David Seki. “Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that.”

Journal Reference:

1. David Seki, Margareta Mayer, Bela Hausmann, Petra Pjevac, Vito Giordano, Katharina Goeral, Lukas Unterasinger, Katrin Klebermaß-Schrehof, Kim De Paepe, Tom Van de Wiele, Andreas Spittler, Gregor Kasprian, Benedikt Warth, Angelika Berger, David Berry, Lukas Wisgrill. Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage. Cell Host & Microbe, 2021; DOI: 10.1016/j.chom.2021.08.004

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AMERICAN HEART ASSOCIATION

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Flavonoid-rich foods, including berries, apples, pears and wine, appear to have a positive effect on blood pressure levels, an association that is partially explained by characteristics of the gut microbiome, according to new research published today in Hypertension, an American Heart Association journal.

“Our gut microbiome plays a key role in metabolizing flavonoids to enhance their cardioprotective effects, and this study provides evidence to suggest these blood pressure-lowering effects are achievable with simple changes to the daily diet,” said lead investigator of the study Aedín Cassidy, Ph.D., chair and professor in nutrition and preventive medicine at the Institute for Global Food Security at Queen’s University in Belfast, Northern Ireland.

Flavonoids are compounds found naturally in fruits, vegetables and plant-based foods such as tea, chocolate and wine, and have been shown in previous research to offer a variety of health benefits to the body. Flavonoids are broken down by the body’s gut microbiome—the bacteria found in the digestive tract. Recent studies found a link between gut microbiota, the microorganisms in the human digestive tract, and cardiovascular disease (CVD), which is the leading cause of death worldwide. Gut microbiota is highly variable between individuals, and there are reported differences in gut microbial compositions among people with and without CVD.

With increased research suggesting flavonoids may reduce heart disease risk, this study assessed the role of the gut microbiome on the process. Researchers examined the association between eating flavonoid-rich foods with blood pressure and gut microbiome diversity. The study also investigated how much variance within the gut microbiome could explain the association between intake of flavonoid-rich foods and blood pressure.

A group of 904 adults between the ages of 25 and 82, 57% men from Germany’s PopGen biobank were recruited for this study. (The PopGen biobank includes participants from a network of seven biobanks in Northern Germany.) Researchers evaluated the participants’ food intake, gut microbiome and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.

Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods. Flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.

Gut microbiome for participants was assessed by fecal bacterial DNA extracted from stool samples. After an overnight fast, participants’ blood pressure levels were measured three times in three-minute intervals after an initial five-minute rest period. Researchers also collected participants’ lifestyle information, including sex, age, smoking status, medication use and physical activity, as well as family history of coronary artery disease, the number of daily calories and fiber consumed, and each participant’s height and weight was measured to calculate BMI (body mass index).

The analysis of regular flavonoid intake with gut microbiome and blood pressure levels found:

• Study participants who had the highest intake of flavonoid-rich foods, including berries, red wine, apples and pears, had lower systolic blood pressure levels, as well as greater diversity in their gut microbiome than the participants who consumed the lowest levels of flavonoid-rich foods.
• Up to 15.2% of the association between flavonoid-rich foods and systolic blood pressure could be explained by the diversity found in participants’ gut microbiome.
• Eating 1.6 servings of berries per day (one serving equals 80 grams, or 1 cup) was associated with an average reduction in systolic blood pressure levels of 4.1 mm Hg, and about 12% of the association was explained by gut microbiome factors.

• Drinking 2.8 glasses (125 ml of wine per glass) of red wine a week was associated with an average of 3.7 mm Hg lower systolic blood pressure level, of which 15% could be explained by the gut microbiome.

“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Cassidy. “A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”

While this study suggests potential benefits to consuming red wine, the American Heart Association suggests that if you don’t drink alcohol already, you shouldn’t start. If you do drink, talk with your doctor about the benefits and risks of consuming alcohol in moderation. According to a statement on dietary health by the American Heart Association, alcohol intake can be a component of a healthy diet if consumed in moderation (no more than one alcoholic drink per day for women and 2 alcohol drinks per day for men) and only by nonpregnant women and adults when there is no risk to existing health conditions, medication-alcohol interaction, or personal safety and work situations.

The authors note that participants for the study were from the general population, and the participants were unaware of the hypothesis. However, residual or unmeasured confounding factors (such as other health conditions or genetics) can lead to bias, thus these findings cannot prove a direct cause and effect, although the researchers did conduct a detailed adjustment in their analyses for a wide range of diet and lifestyle factors. The authors noted the focus of this study was on specific foods rich in flavonoids, not all food and beverages with flavonoids.

Co-authors are first author Amy Jennings, Ph.D.; Manja Koch, Ph.D.; Corinna Bang, Ph.D.; Andre Franke, Ph.D.; and Wolfgang Lieb, M.D., M.Sc. The authors’ disclosures are listed in the manuscript.

The research was funded by grants from the German Research Foundation and the German Federal Ministry of Education and Research. The PopGen biobank is supported by the German Federal Ministry of Education and Research and the Medical Faculty of the University of Kiel.

10.1161/HYPERTENSIONAHA.121.17441

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