Field Notes
Obese and Overweight Children at Risk of Iron Deficiency
Children and young people who are overweight or obese are at significantly higher risk of iron deficiency, according to a study by nutritional scientists at the University of Leeds.
Researchers from the School of Food Science and Nutrition examined thousands of medical studies from 44 countries involving people under the age of 25 where levels of iron and other vitamins and minerals had been recorded alongside weight.
They found that iron deficiency was associated with both underweight and overweight children and adolescents.
By contrast, zinc and vitamin A deficiencies were only observed in children who were undernourished, leading researchers to conclude that iron deficiency in overweight children is possibly due to inflammation disrupting the mechanisms that regulate iron absorption.
The results of the study, which was funded by the UK Biotechnology and Biological Sciences Research Council, were published in the journal BMJ GlobalHealth.
Iron deficiency in children has a negative effect on brain function, including attention, concentration, and memory, and can increase the risk of conditions such as autism and ADHD.
Iron deficiency is already recognized as a problem in adults living with obesity, but this research is the first to look at the association in children.
Lead author Xiaomian Tan, MSc, a doctoral researcher at the University of Leeds' School of Food Science and Nutrition, states: "The relationship between undernutrition and critical micronutrients for childhood growth and development is well established, but less is known about the risk of deficiencies in iron, vitamin A, and zinc in children and adolescents who are overweight or obese, making this a hidden form of malnutrition.
"Our research is hugely important given the high prevalence of obesity in children. We hope it will lead to increased recognition of the problem by health care practitioners and improvements in clinical practice and care."
Hidden Hunger
Historically the problem has been linked to malnutrition and is a particular concern for lower- and middle-income countries where hunger may be the leading cause of mortality for young children.
However, it is increasingly recognized that vitamin and mineral deficiencies can occur in people who are overweight and obese and who have a nutrient-poor but energy-dense diet, at times described as “hidden hunger.”
In high-income countries, this may be associated with ultra-processed foods that are high in fat, sugar, salt, and energy, but in lower- and middle-income countries, obesity is often associated with poverty and monotonous diets with limited choices of staples such as corn, wheat, rice, and potatoes.
Many developing countries are now facing a double burden of malnutrition alongside overnutrition due to the rapid increase in the global prevalence of obesity in recent decades, especially in children aged between 5 and 19.
Undernutrition vs Overnutrition
The research also highlights differences in focus between higher-income countries and developing nations, with most studies in Africa and Asia focusing on undernutrition and those from North America and Europe focusing more on overnutrition.
The researchers say this is particularly concerning as both Africa and Asia are experiencing the highest double burden of malnutrition due to economic growth and the transition to a Western-style high-sugar, high-fat diet.
Between the years 2000 and 2017, the number of overweight children under the age of 5 in Africa increased from 6.6 to 9.7 million, and in Asia, that figure rose from 13.9 to 17.5 million. At the same time, there was an increase in the number of stunted children under 5, from 50.6 to 58.7 million in Africa.
Research supervisor Bernadette Moore, PhD, a professor of nutritional sciences at Leeds' School of Food Science and Nutrition, explains: "These stark figures underscore the fact that the investigation of micronutrient deficiencies in relation to the double burden of malnutrition remains critically important for child health.
"By the age of 11 in the UK, one in three children are living with overweight or obesity, and our data suggests that even in overweight children inflammation leading to iron deficiency can be an issue.
"Iron status may be the canary in the coal mine, but the real issue is that prolonged inflammation leads to heart disease, diabetes, and fatty liver."
Increasing physical activity and improving diet have been shown to reduce inflammation and improve iron status in children, and the researchers are now calling for further studies into the effectiveness of these interventions.
They also believe that more research into micronutrient deficiencies and the double burden of malnutrition and overnutrition in countries where there are currently gaps in data is needed.
— Source: University of Leeds
Scientists Link Certain Gut Bacteria to Lower Heart Disease Risk
Changes in the gut microbiome are implicated in a range of diseases, including type 2 diabetes, obesity, and inflammatory bowel disease. A team of researchers at the Broad Institute of MIT and Harvard, along with Massachusetts General Hospital, have found that microbes in the gut may affect CVD risk as well. In a study published in Cell, researchers identified specific species of bacteria that consume cholesterol in the gut and may help lower cholesterol and heart disease risk in people.
Researchers analyzed metabolites and microbial genomes from more than 1,400 participants in the Framingham Heart Study, a decades-long project focused on risk factors for CVD. The team discovered that bacteria called Oscillibacter metabolize 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 possible mechanism the bacteria 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 microbiome changes 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,” says Ramnik Xavier, MD, a core institute member, director of the immunology program, and codirector of the infectious disease and microbiome program at the Broad. Xavier is also a professor at Harvard Medical School and Massachusetts General Hospital.
Postdoctoral researcher Chenhao Li, PhD, MSc, and research scientist Martin Stražar, PhD, both in Xavier’s lab, were coauthors of the study.
Cholesterol Cues
In the past decade, other researchers have uncovered links between the composition of the gut microbiome and elements of CVD, 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 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 says. “That allowed us to note effects that are really subtle and hard to measure and directly follow up on them.”
The approach uncovered more than 16,000 associations between microbes and metabolic traits, including one that was 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, one 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 use to lower cholesterol levels. They found that the bacteria converted cholesterol into intermediate products that are 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 scientists had previously shown to be 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 investigating combinations of bacterial species could help shed light on how different microbial communities interact to affect human health.
Microbial Messages
The vast majority of genes in the human gut microbiome remains uncharacterized, but the team is confident that their success in pinpointing cholesterol-metabolizing enzymes paves 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 fecal microbiome transfer without much understanding of how the microbes interact with each other and the gut,” Li says. “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 adds. “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