Health is wealth as the saying goes and new research now shows that it is possible to have a healthy, less stressed society through familiar and inexpensive foods. One such food might be the Japanese natto which is made from softened soybeans that have been boiled or steamed and fermented with a bacteria called Bacillus subtilis var. natto. Bacillus subtilis var. natto is found in soil, plants, animals, and the human stomach and intestines. Most of the natto consumed in Japan is made from the Miyagino strain.
A research group led by Professor Eriko Kage-Nakadai at the Graduate School of Human Life and Ecology, Osaka Metropolitan University, examined the effects of Bacillus subtilis var. natto consumption on the lifespan of the host using Caenorhabditis elegans worms. The researchers found that Caenorhabditis elegans fed Bacillus subtilis var. natto had a significantly longer lifespan than those fed the standard diet, and further elucidated that the p38 MAPK pathway and insulin/IGF-1-like signaling pathway, which are known to be involved in innate immunity and lifespan, were involved in the lifespan-enhancing effects of Bacillus subtilis var. natto. They also examined stress tolerance, which has been shown to have a correlation with longevity, and found that resistance to UV light and oxidative stress is enhanced.
For the first time, we were able to demonstrate the possibility of lifespan-extending effects of Caenorhabditis elegans through the ingestion of Bacillus subtilis var. natto. We hope that future experiments on mammals and epidemiological studies will help to realize a healthy and longer-living society if we can apply this research to humans.”
Professor Eriko Kage-Nakadai, Graduate School of Human Life and Ecology, Osaka Metropolitan University
The research results were published online in the Journal of Applied Microbiology on April 20, 2023.
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Teramoto, N., et al. (2023) Impacts of Bacillus subtilis var. natto on the lifespan and stress resistance of Caenorhabditis elegans.Journal of Applied Microbiology. doi.org/10.1093/jambio/lxad082.
A new paper published in the Frontiers in Microbiology explores the contribution of human breast milk to the establishment of the infant gut microbiome.
Breastfeeding is encouraged as the first and exclusive food of infants for at least the first six months of life. In addition to its nutritional content, breast milk contributes significantly to the formation of the infant gut microbiome. This is because of its high content of immune cells, oligosaccharides carrying glycosyl residues, fatty acids, and some microbes.
Both breast milk bacteria and skin microbes from the maternal nipple reach and establish themselves in the infant’s gut. Bacteria may be shielded by secretory immunoglobulin A (sIgA) covering the immune system, thus allowing them to enter the gut intact.
The infant gut microbiome (IGMB) is important for both infant development and immunity, as well as modulating conditions like atopy and body mass composition. However, earlier research on potential associations between the IGMB and breast milk microbiota has been limited to analyzing samples from corresponding time points.
The current study included almost 190 dyads from New Hampshire. Breast milk and infant stool samples were collected at around six weeks, four months, six months, nine months, and one year from birth, which allowed the scientists to identify correlations that developed over time.
What did the study show?
In the study population, with a mean age of 32 years, most were White and had a normal body mass index (BMI) during pregnancy. About 25% of deliveries occurred through Cesarean section (C-section), and antibiotic exposure prior to lactation occurred in over half of mothers.
Most babies were almost full term at birth, with only 3% being exposed to antibiotics by four months of life. By one year, about 30% of infants had been exposed to antibiotics.
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About 75% and 40% of infants did not receive any formula up to six weeks and four months, respectively. Most infants began eating solid food by six months.
Three breast milk microbiome types (BMTs) were identified in the six-week breast milk samples. These could be differentiated by the relative proportions of four bacterial genera, including Streptococcus, Staphylococcus, Pseudomonas, and Acinetobacter, as well as by the microbial diversity.
At six weeks, the gut microbiome in infants exhibited four six-week infant gut microbiome types (6wIGMTs). These had different abundances of Bifidobacterium, Bacteroides, Clostridium, Streptococcus, and Escherichia/Shigella.
The 6wIGMT correlated with the 6wBMT in male infants and those born by C-section. Notably, the same microbe was likely to be the most abundant within the dyads at this point.
By age one, the predominant difference in microbiome composition was due to Bacteroides. There was no association between the 6wBMT and 12mIGMT, which is likely due to the intake of solid foods by infants at this age. The transition to a primarily solid diet causes the infant microbiome to be dominated by other microbes, such as Bifidobacterium and Bacteroidetes, both of which are more abundant in the adult gut.
At six weeks, the BMT was associated with 6wIGMT in all infants but more strongly in male infants born by C-section. Male infants also had a higher proportion of microbes from breast milk present in their stool.
While infants delivered by C-section have a reduced colonization by maternal stool microbiota, their colonization by breast milk microbiota is higher than vaginally delivered infants.”
This could be due to the reduced microbial diversity and Bacteroides depletion in the IGMB of C-section-delivered infants, which makes it easier for breast milk microbes to colonize the gut.
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Male infants appeared to show a greater effect of the breast milk microbes on their gut microbiome. This may be because they exhibit less microbial diversity, with fewer Clostridiales and more Enterobacteriales abundance than is observed in female infants. The male infant’s gut microbiota is also more susceptible to stress and environmental exposures.
Overall, the breast milk microbial communities correlated most strongly with those found in infant stool samples that were collected at a later time point. For example, Pantoea in breast milk at four and six months was correlated with infant stool collected at nine and twelve months, respectively. These findings require further validation in future research.
What are the implications?
The identification of microbial clusters in human milk and infant feces that were shared within the mother-infant pair at six weeks is a striking finding in this study. The delay in cluster sharing and the association with C-section were associated with stronger correlations.
The findings of this study agree with earlier reports on the associations of various microbes in breast milk and the infant gut. Notably, the current study adds to previous data by identifying correlations between different taxa in these two sites.
The scientists postulate that microbes within communities may show direct interactions, such as the transmission of a microbe present in the infant oral cavity to the breast in this case, as well as the intake of breast milk by the infant. In addition, they may show indirect interactions through nutrients like fatty acids and milk sugars or other bacterial metabolites that influence both communities.
With the observed shift in breast milk microbial diversity over time, long-term studies may be needed to understand the breadth of microbial exposures during infancy. The change in IGMTs over time should also be better characterized and their relevance assessed.
These results suggest that milk microbial communities have a long-term effect on the infant gut microbiome both through sharing of microbes and other molecular mechanisms.”
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Journal reference:
Lundgren, S. N., Madan, J. C., Karagas, M. R., et al. (2023). Human milk-associated bacterial communities associate with the infant gut microbiome over the first year of life. Frontiers in Microbiology. doi:10.3389/fmicb.2023.1164553.
Contrary to common belief, anorexia nervosa is not just a desire to be skinny. Rather, it is a complicated mental illness that alters the brain’s control over hunger and self-perception of one’s body.
Individuals with anorexia nervosa experience a transformation in their brain’s reward mechanism, making weight loss their primary focus. This results in drastic behavioral changes, including a drastic reduction in caloric intake. Approximately 1% of young people develop anorexia nervosa, and for about one in five, it becomes a chronic and potentially fatal condition. The majority of those diagnosed with anorexia nervosa are young females in their teenage years or early adulthood, accounting for about 90% of cases.
The incidence of anorexia nervosa is too upward.
The disease is caused by a complex interaction between various so-called vulnerability genes and environmental influences. However, it now also appears to be a result of a severe imbalance in the intestinal ecosystem of trillions of bacteria and viruses.
This is the conclusion of a new study conducted by an international team headed by Danish scientists. The study involved 77 Danish girls and young women suffering from anorexia nervosa and 70 healthy individuals of the same gender. The results suggest that severe changes in the intestinal microbes and corresponding gut microbiome-produced metabolites in the blood may directly affect the development and retention of anorexia nervosa.
To demonstrate this, the researchers transplanted stools from anorexia cases and healthy individuals, respectively, to bacteria-free mice, explains Professor and Principal Investigator Oluf Borbye Pedersen from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.
“The mice receiving stools from individuals with anorexia nervosa had trouble gaining weight, and analyses of gene activities in certain parts of their brain revealed changes in various genes regulating appetite. In addition, the mice that had been given stools from individuals affected with anorexia nervosa showed increased activity of genes regulating fat combustion likely contributing to their lower body weight,” explains Oluf Pedersen, who is the lead investigator of the study together with Clinical Professor René Støvring, who specializes in anorexia nervosa.
Using DNA technology and advanced bioinformatics analyses, the researchers identified distinct and marked changes in the composition and function of the intestines’ trillions of bacteria and viruses in cases with anorexia nervosa.
Researchers compared the disruptions of the gut microbiome with blood molecules (metabolites) produced by the gut microbiome demonstrating associations between specific changes of the gut bacteria, blood bacterial molecules, and a number of personality traits such as distorted body image, drive for thinness, and refusal to eat in those affected by anorexia nervosa.
“We also discovered that specific gut bacteria in women with anorexia nervosa produce less vitamin B1. Deficiency of B1 may lead to loss of appetite, various intestinal symptoms, anxiety, and isolating social behavior,” says Assistant Professor Yong Fan from the Novo Nordisk Foundation Center for Basic Metabolic Research, a leading young researcher of the study.
“Moreover, our analysis of the intestinal microbiome revealed in anorexia cases different virus particles able to decompose lactic acid-producing bacteria in the intestines. Both findings may form the basis of future clinically controlled trials with B1 vitamin supplements and fermented food or probiotics containing various types of lactic acid bacteria,” he says.
The new study is an example of basic research meant to explore whether a disturbed microbial ecosystem of the gut is a contributory factor in the development or retention of a chronic disease. And this may potentially be the case for anorexia nervosa.
The next question is whether basic research can lay the foundation for clinically controlled trials exploring if current treatment for anorexia nervosa – involving psychotherapy, family counseling, and attempts to change the patient’s eating and exercise habits – may benefit from additional treatment aimed at normalizing the intestinal microbiome.
“A complex disease like anorexia nervosa calls for personalized and multifactorial treatment. Our findings suggest that disruptions of the communities of gut bacteria and viruses and their functions as mirrored in altered microbiome-synthesized blood metabolites may be involved in the development and retention of the disease, providing a rationale for initiating clinically controlled trials. In such trials, clinical investigators will likely test the potential effects of an initial antibiotics intervention to reset the aberrant gut microbiome followed by weekly fecal microbiota transplantation (FMT) from young healthy donors for months. Such FMTs might be supplemented with B1 vitamin and multistrain probiotics. Whether interventions like the suggested will qualify for future adjunctive therapy to current conventional intervention, remain to be shown”, says Oluf Pedersen.
Reference: “The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice” by Yong Fan, René Klinkby Støving, Samar Berreira Ibraim, Tuulia Hyötyläinen, Florence Thirion, Tulika Arora, Liwei Lyu, Evelina Stankevic, Tue Haldor Hansen, Pierre Déchelotte, Tim Sinioja, Oddny Ragnarsdottir, Nicolas Pons, Nathalie Galleron, Benoît Quinquis, Florence Levenez, Hugo Roume, Gwen Falony, Sara Vieira-Silva, Jeroen Raes, Loa Clausen, Gry Kjaersdam Telléus, Fredrik Bäckhed, Matej Oresic, S. Dusko Ehrlich and Oluf Pedersen, 17 April 2023, Nature Microbiology. DOI: 10.1038/s41564-023-01355-5
The international research team comprised Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, the University of Southern Denmark and Odense University Hospital, Aalborg University Hospital, Aarhus University Hospital, the National Research Institute for Agriculture, Food and Environment in France, Center for Microbiology, VIB, Leuven, Belgium, University of Gothenburg and Ørebro University in Sweden, Turku University in Finland and Leiden University in the Netherlands.
University of Copenhagen – The Faculty of Health and Medical Sciences
Researchers at Umeå University, Sweden, have found that among the many factors that shape the intestinal microbiota composition, diet has a much stronger impact than defensins, which are intestinal defence molecules produced by the body. Instead, they identified a possible role for these molecules in preventing increased blood glucose levels after consumption of high-caloric “Western-style diet”.
While the effect of defensins in shaping the adult microbiota composition is rather minor when compared to diet, defensins still have a very important role in protecting us against microbial infections; and our research highlights their protective role against the metabolic complications that can arise after the intake of a high-fat and high-sugar Western-style diet.”
Fabiola Puértolas Balint, PhD Student at the Department of Molecular Biology at Umeå University
She is working in Björn Schröder’s research group, which is also affiliated to Umeå Centre of Microbial Research, UCMR, and The Laboratory for Molecular Infection Medicine Sweden, MIMS, at Umeå University.
The gut microbiota refers to the community of trillions of microorganisms that live inside everyone’s gut. Over the past decades, the abundance of specific bacteria in this community has been extensively studied due to its connection to many diseases, including inflammatory bowel diseases, obesity and diabetes, and even psychological disorders. The microbial community is seeded during birth, after which several internal and external factors help shaping the community to its final composition. These factors include, among others, diet (especially fibre), genetics, medication, exercise, and defence molecules, the so-called antimicrobial peptides.
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Antimicrobial peptides can be regarded as the body´s own naturally produced antibiotic molecules. In particular, the largest group of antimicrobial peptides – the defensins – is produced by all body surfaces, including the skin, the lungs and the gastrointestinal tract. Defensins are considered the immune system´s first line of defence against infections but at the same time they have also been thought to be essential in shaping the microbiota composition in the small intestine. However, it was so far unclear how big their effect was as compared to diet, which is known to have a major impact.
To investigate this, the researchers from Björn Schröder lab used normal healthy mice and compared their microbiota composition in the small intestine to mice that could not produce functional defensins in the gut, and then both mouse groups were fed either a healthy diet or a low-fibre Western-style diet.
“When we analysed the microbiota composition inside the gut and at the gut wall of two different regions in the small intestine, we were surprised – and slightly disappointed – that defensins had only a very minor effect on shaping the overall microbiota composition,” says Björn Schröder.
However, the intestinal defensins still had some effect directly at the gut wall, where the defensins are produced and secreted. Here, a few distinct bacteria seemed to be affected by the presence of defensins, among them Dubosiella and Bifidobacteria, likely due to selective antimicrobial activity of the defensins.
“To our surprise, we also found that the combination of eating a Western-style diet and lacking functional defensins led to increased fasting blood glucose values, which indicated that defensins may help to protect against metabolic disorders when eating an unhealthy diet,” says Björn Schröder.
The results suggest that strategies that aim to positively modulate the microbiota composition should rather focus on diet, as modulation of the composition via increased production of own host defense molecules, such as defensins, may have only a small impact on the overall composition. However, it is possible that especially early in life, when the microbiota community is not fully matured yet, defensins may have a stronger effect on the microbial composition. Still, increasing the production of defensins may be a valuable option to prevent the development of metabolic disorders.
The results have been published in the scientific journal Microbiology Spectrum.
Puértolas-Balint, F., & Schroeder, B. O. (2023). Intestinal α-Defensins Play a Minor Role in Modulating the Small Intestinal Microbiota Composition as Compared to Diet. Microbiology Spectrum. doi.org/10.1128/spectrum.00567-23.
In an article published in the journal Current Opinion in Microbiology, scientists have provided a detailed overview of the factors affecting maternal gut microbiota during pregnancy and its impact on maternal and infant health.
Pregnancy is associated with a wide range of hormonal, immunological, and metabolic changes needed for fetal development. The most notable changes include increased cardiac output, higher levels of T regulatory cells, and alteration in gut microbiome composition.
Alteration in gut microbiota composition and diversity is associated with changes in women’s metabolic, immunological, and neurological processes, irrespective of pregnancy status. In addition, changes in gut microbiota composition are known to affect insulin sensitivity. In children with type 1 diabetes, functional and metabolic changes in gut microbiota have been documented.
Alteration in gut microbiota during pregnancy
Only limited evidence is available to thoroughly understand the changes in gut microbiota during pregnancy and its impact on maternal and fetal health. However, according to the available literature, low-grade inflammation at the intestinal mucosa as well as hormonal changes, might be responsible for gut microbiota alteration during pregnancy.
Regarding hormonal changes, pregnancy-related induction in progesterone levels is known to directly associate with increased Bifidobacterium levels in women. Bifidobacterium is a beneficial bacterium that naturally resides in the intestine. Therefore, the gut-to-gut transmission of this bacterium from the mother to the infant is crucial during the neonatal period. In infants, this bacterium helps degrade human milk oligosaccharides coming from maternal milk, in addition to developing infant gut microbiota and immune system.
Factors influencing maternal gut microbiota during pregnancy
Adult human gut microbiota can be influenced by many factors, including body mass index (BMI), medications, diseases, environment, and lifestyle (diet, physical activity, smoking, and drinking habits). Pre-pregnancy exposure to these factors can lead to structural and functional alteration in maternal gut microbiota during pregnancy.
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Animal studies have shown that maternal diet influences maternal and infant gut microbiota composition before and during pregnancy. Both pre-pregnancy body weight and pregnancy-related weight gain have been found to alter the composition and diversity of maternal gut microbiota.
Infant gut microbiota are influenced by the way they are delivered. For example, infants delivered vaginally have been shown to gain beneficial changes in gut microbiota compared to those delivered by c-section.
Functional studies in animals have shown that smoking-related nicotine exposure during pregnancy affects maternal gut microbiota, which in turn alters fetal exposure levels to circulating short-chain fatty acids and leptin during in-utero development.
Certain diseases before pregnancy, such as inflammatory bowel disease, have been found to influence maternal microbiota during pregnancy. The microbiota of the pregnant mother’s gut has also been shown to be affected pre-pregnancy and during pregnancy by certain medications, including antibiotics, proton-pump inhibitors, metformin, laxatives, and probiotics.
Maternal health impact of altered gut microbiota
Studies have found maternal gut microbiota alteration during pregnancy is associated with pregnancy complications, including gestational diabetes and preeclampsia.
Gestational diabetes
A spontaneous induction in blood glucose levels during pregnancy is medically termed gestational diabetes. Studies have shown that a reduced abundance of beneficial bacteria and an increased abundance of pathogenic bacteria are responsible for the onset of gestational diabetes.
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In the microbiome of gestational diabetes patients, an increased abundance of membrane transport, energy metabolism, lipopolysaccharides, and phosphotransferase system pathways has been observed. Recent evidence indicates that gut microbiota-derived dopamine deficiency in the blood, impaired production of short-chain fatty acids, and excessive metabolic inflammation are collectively responsible for the development of gestational diabetes.
Preeclampsia
Preeclampsia is characterized by new-onset hypertension, proteinuria, and organ dysfunction during pregnancy. Studies involving pregnant women with preeclampsia have found gut microbiota dysbiosis (imbalance in gut microbiota composition) and increased plasma levels of lipopolysaccharide and trimethylamine N-oxide.
Recent evidence indicates that preeclampsia onset is associated with reduced bacterial diversity in gut microbiota. Specifically, the changes in gut microbiota include a depletion in beneficial bacteria and an enrichment in opportunistic bacteria.
Some mechanistic studies have pointed out that gut microbiota dysbiosis induces immune imbalance and intestinal barrier disruption in pregnant women, leading to the translocation of bacteria to the intrauterine cavity, placental inflammation, and poor placentation. All these factors collectively contribute to the development of preeclampsia.
Infant health impact of altered gut microbiota
Alteration in maternal gut microbiota has been found to affect the fetus’s neurodevelopment via signaling microbially modulated metabolites to neurons in the developing brain. These changes can have long-term effects on an infant’s behaviors.
Maternal microbiota-derived metabolites such as short-chain fatty acids are known to shape the metabolic system of infants. Some evidence has also indicated that maternal gut microbiota influences an infant’s susceptibility to allergic diseases.
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In an article published in the journal Current Opinion in Microbiology, scientists have provided a detailed overview of the factors affecting maternal gut microbiota during pregnancy and its impact on maternal and infant health.
Pregnancy is associated with a wide range of hormonal, immunological, and metabolic changes needed for fetal development. The most notable changes include increased cardiac output, higher levels of T regulatory cells, and alteration in gut microbiome composition.
Alteration in gut microbiota composition and diversity is associated with changes in women’s metabolic, immunological, and neurological processes, irrespective of pregnancy status. In addition, changes in gut microbiota composition are known to affect insulin sensitivity. In children with type 1 diabetes, functional and metabolic changes in gut microbiota have been documented.
Alteration in gut microbiota during pregnancy
Only limited evidence is available to thoroughly understand the changes in gut microbiota during pregnancy and its impact on maternal and fetal health. However, according to the available literature, low-grade inflammation at the intestinal mucosa as well as hormonal changes, might be responsible for gut microbiota alteration during pregnancy.
Regarding hormonal changes, pregnancy-related induction in progesterone levels is known to directly associate with increased Bifidobacterium levels in women. Bifidobacterium is a beneficial bacterium that naturally resides in the intestine. Therefore, the gut-to-gut transmission of this bacterium from the mother to the infant is crucial during the neonatal period. In infants, this bacterium helps degrade human milk oligosaccharides coming from maternal milk, in addition to developing infant gut microbiota and immune system.
Factors influencing maternal gut microbiota during pregnancy
Adult human gut microbiota can be influenced by many factors, including body mass index (BMI), medications, diseases, environment, and lifestyle (diet, physical activity, smoking, and drinking habits). Pre-pregnancy exposure to these factors can lead to structural and functional alteration in maternal gut microbiota during pregnancy.
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Animal studies have shown that maternal diet influences maternal and infant gut microbiota composition before and during pregnancy. Both pre-pregnancy body weight and pregnancy-related weight gain have been found to alter the composition and diversity of maternal gut microbiota.
Mode of delivery has been found to influence infant gut microbiota. For example, infants delivered vaginally have been shown to gain beneficial changes in gut microbiota compared to those delivered by c-section.
Functional studies in animals have shown that smoking-related nicotine exposure during pregnancy affects maternal gut microbiota, which in turn alters fetal exposure levels to circulating short-chain fatty acids and leptin during in-utero development.
Certain diseases before pregnancy, such as inflammatory bowel disease, have been found to influence maternal microbiota during pregnancy. Similarly, pre-pregnancy and during-pregnancy consumption of certain medications, including antibiotics, proton-pump inhibitors, metformin, laxatives, and probiotics, has been found to influence maternal gut microbiota during pregnancy.
Maternal health impact of altered gut microbiota
Studies have found maternal gut microbiota alteration during pregnancy is associated with pregnancy complications, including gestational diabetes and preeclampsia.
Gestational diabetes
A spontaneous induction in blood glucose levels during pregnancy is medically termed gestational diabetes. Studies have shown that a reduced abundance of beneficial bacteria and an increased abundance of pathogenic bacteria are responsible for the onset of gestational diabetes.
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In the microbiome of gestational diabetes patients, an increased abundance of membrane transport, energy metabolism, lipopolysaccharides, and phosphotransferase system pathways has been observed. Recent evidence indicates that gut microbiota-derived dopamine deficiency in the blood, impaired production of short-chain fatty acids, and excessive metabolic inflammation are collectively responsible for the development of gestational diabetes.
Preeclampsia
Preeclampsia is characterized by new-onset hypertension, proteinuria, and organ dysfunction during pregnancy. Studies involving pregnant women with preeclampsia have found gut microbiota dysbiosis (imbalance in gut microbiota composition) and increased plasma levels of lipopolysaccharide and trimethylamine N-oxide.
Recent evidence indicates that preeclampsia onset is associated with reduced bacterial diversity in gut microbiota. Specifically, the changes in gut microbiota include a depletion in beneficial bacteria and an enrichment in opportunistic bacteria.
Some mechanistic studies have pointed out that gut microbiota dysbiosis induces immune imbalance and intestinal barrier disruption in pregnant women, leading to the translocation of bacteria to the intrauterine cavity, placental inflammation, and poor placentation. All these factors collectively contribute to the development of preeclampsia.
Infant health impact of altered gut microbiota
Alteration in maternal gut microbiota has been found to affect the fetus’s neurodevelopment via signaling microbially modulated metabolites to neurons in the developing brain. These changes can have long-term effects on an infant’s behaviors.
Maternal microbiota-derived metabolites such as short-chain fatty acids are known to shape the metabolic system of infants. Some evidence has also indicated that maternal gut microbiota influences an infant’s susceptibility to allergic diseases.
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New research from the University of Missouri School of Medicine has established a link between western diets high in fat and sugar and the development of non-alcoholic fatty liver disease, the leading cause of chronic liver disease.
The research, based in the Roy Blunt NextGen Precision Health Building at MU, has identified the western diet-induced microbial and metabolic contributors to liver disease, advancing our understanding of the gut-liver axis, and in turn the development of dietary and microbial interventions for this global health threat.
We’re just beginning to understand how food and gut microbiota interact to produce metabolites that contribute to the development of liver disease. However, the specific bacteria and metabolites, as well as the underlying mechanisms were not well understood until now. This research is unlocking the how and why.”
Guangfu Li, PhD, DVM, co-principal investigator, associate professor in the department of surgery and Department of Molecular Microbiology and Immunology
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The gut and liver have a close anatomical and functional connection via the portal vein. Unhealthy diets change the gut microbiota, resulting in the production of pathogenic factors that impact the liver. By feeding mice foods high in fat and sugar, the research team discovered that the mice developed a gut bacteria called Blautia producta and a lipid that caused liver inflammation and fibrosis. That, in turn, caused the mice to develop non-alcoholic steatohepatitis or fatty liver disease, with similar features to the human disease.
“Fatty liver disease is a global health epidemic,” said Kevin Staveley-O’Carroll, MD, PhD, professor in the department of surgery, one of the lead researchers. “Not only is it becoming the leading cause of liver cancer and cirrhosis, but many patients I see with other cancers have fatty liver disease and don’t even know it. Often, this makes it impossible for them to undergo potentially curative surgery for their other cancers.”
As part of this study, the researchers tested treating the mice with an antibiotic cocktail administered via drinking water. They found that the antibiotic treatment reduced liver inflammation and lipid accumulation, resulting in a reduction in fatty liver disease. These results suggest that antibiotic-induced changes in the gut microbiota can suppress inflammatory responses and liver fibrosis.
Li, Staveley-O’Carroll and fellow co-principal investigator R. Scott Rector, PhD, Director of NextGen Precision Health Building and Interim Senior Associate Dean for Research -; are part of NextGen Precision Health, an initiative to expand collaboration in personalized health care and the translation of interdisciplinary research for the benefit of society. The team recently received a $1.2 million grant from the National Institutes of Health to fund this ongoing research into the link between gut bacteria and liver disease.
Yang, M., et al. (2023). Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol. Nature Communications. doi.org/10.1038/s41467-023-35861-1.
According to a recent study by scientists at Cornell and Binghamton University, metal oxide nanoparticles which are frequently utilized as food coloring and anti-caking agents in the food industry, may cause damage to certain sections of the human intestine.
“We found that specific nanoparticles – titanium dioxide and silicon dioxide – ordinarily used in food may negatively affect intestinal functionality,” said senior author Elad Tako, associate professor of food science at Cornell. “They have a negative effect on key digestive and absorptive proteins.”
In their study, the research team administered human-equivalent doses of titanium dioxide and silicon dioxide in the Tako laboratory’s in vivo system, which provides a health response that closely resembles that of the human body.
The scientists injected the nanoparticles into chicken eggs. After the chickens hatched, the scientists detected changes in the functional, morphological, and microbial biomarkers in the blood, the duodenum (upper intestine), and the cecum (a pouch connected to the intestine).
“We are consuming these nanoparticles on a daily basis,” said Tako. “We don’t really know how much we consume; we don’t really know the long-term effects of this consumption. Here, we were able to demonstrate some of these effects, which is a key to understanding gastrointestinal health and development.”
Despite the finding, the scientists are not yet calling for an end to the use of these nanoparticles.
“Based on the information, we suggest simply being aware,” Tako said. “Science needs to conduct further investigations based on our findings. We are opening the door for discussion.”
Reference: “Food-Grade Metal Oxide Nanoparticles Exposure Alters Intestinal Microbial Populations, Brush Border Membrane Functionality and Morphology, In Vivo (Gallus gallus)” by Jacquelyn Cheng, Nikolai Kolba, Alba García-Rodríguez, Cláudia N. H. Marques, Gretchen J. Mahler and Elad Tako, 9 February 2023, Antioxidants. DOI: 10.3390/antiox12020431
The study was funded by the National Institutes of Health.
Nanoparticles are used in food colorings to improve their stability, solubility, and color intensity. Food coloring nanoparticles are made by reducing the size of color particles to the nanoscale range, typically between 1 and 100 nanometers in diameter.
Nanoparticles have a larger surface area than larger particles, which makes them more reactive and improves their ability to disperse in food. This improved dispersion leads to better color stability, as the nanoparticles are less likely to clump together or settle out of the food product.
In addition to stability, nanoparticles can also enhance the intensity of food colors. This is because the smaller size of the particles allows them to interact more efficiently with light, resulting in more vivid and intense colors.
However, it is important to note that the use of nanoparticles in food has raised concerns about their potential health effects. As a result, regulatory bodies such as the U.S. Food and Drug Administration (FDA) require that food manufacturers provide evidence that the nanoparticles they use are safe for consumption.
In a recent review published in Current Opinion in Microbiology, researchers reviewed existing data on variations in human microbiota, emphasizing on ageing- and ethnicity-associated changes in the microbiota.
Human microbial heterogeneity lays the foundation for precision therapeutics, and thus, the potential of personalized microbiota-based diagnostic and therapeutic strategies can be tapped fully by understanding human microbial variations. However, the factors associated with alterations in the human microbiome have yet to be well-characterized.
Further, most of the human microbiota data has been obtained from residents of westernized and socioeconomically developed nations, with the probable skewing of microbiota variations and their associations with health. Moreover, the under-sampling of ethnic minorities in microbiota analyses must be addressed for assessing the history, context, and evolving dynamics of the human microbiota in the context of disease risks.
About the review
In the present review, researchers highlighted recent advances in characterizing human microbiota variations associated with ageing and various ethnicities globally.
Age-related changes in the microbiota of humans
Factors that shape the human microbiota include birth type, family sizes, cohabitation, housing, domestic animals, age, sex, physical fitness, diet, antibiotics, non-antibiotic drugs, and alcohol intake. At the societal level, complex associations of health inequalities, socioeconomic status, and social networks with the human microbiome balance have been reported.
Studies have demonstrated an inverse association between the microbiota and an individual’s age, and conversely, microbial compositional variations contribute to the process of ageing and age-associated diseases. All individuals do not age uniformly, and the differential ageing rates reflect in the human microbiota. Therefore, the human microbiota abundance is evolving as a biomarker to evaluate differences in the biological age and chronological age and between health and disease. Human microbiomes lacking Bacteroides species have been strongly associated with a healthy type of ageing.
Other factors related to variations in the human microbiota composition
Mediterranean diets, involving reduced intake of saturated-type fats, red meat, and milk products, with high consumption of fruits, vegetables, fish, legumes, nuts, and olive oil, have been reported to reverse age-associated microbiota alterations and delay cognitive decline. Studies have reported the co-evolution of human beings and intestinal microbes, with notable variations in Helicobacter pylori diversity associated with human migration.
Microbiome compositions vary among individuals residing in industrialized or non-industrialized regions. Non-industrialized region-associated microbiomes or ancestral microbes have adapted to metabolizing complex-type carbohydrates from diets with high fibre content. The microbial compositions vary by season, climatic fluctuations, and accessibility to unprocessed-type foods. The microbiome of individuals living in non-industrialized regions reportedly has lower Bacteroides/Prevotella spp. ratio, elevated counts of Treponema species, and varying abundance of parasites that affect the immunity of the host.
Naturally maintained palaeofaeces microbiome genomes resemble the genomes of non-industrialized human intestinal microbiota. Socioeconomic developments and industrialization have been associated with microbiome diversity losses, lowered parasitism, reduced counts of ancestral microbes like Helicobacter pylori species and elevated counts of microbes associated with non-communicable and chronic metabolic and inflammatory diseases.
Immigration has been related to an increased abundance of microbes associated with obesity. A study on Irish travellers reported three key factors influencing the human microbiota composition, i.e., living conditions, closeness to domestic pets during childhood and family sizes, with the average number of siblings among traveller families and other families being 10, and one, respectively).
Conclusions
Based on the review findings, the human microbiome is influenced by age, diet, ethnicity and immigration. Further research is required to improve understanding of age-related microbiome changes to identify targets and develop tailored microbiota-based therapeutic interventions. The increase or decrease in microbial abundance associated with changes in dietary patterns and modernization needs to be assessed further to develop highly specific precision medicine catered to the residential locations and food consumed.
The co-diversification of microbes with humans globally warrants in-depth analysis of microbial compositions by ethnicity, region, diet, and industrialization status to maximize the benefit of microbiota-based interventions to one and all. Microbial analyses were performed to evaluate the risk of disease in relation to microbiome dysbiosis and abrupt changes following immigration could inform policy-makers and decision-making and aid in developing personalized therapeutics to improve the standard of care for all individuals across the globe.
In a recent study published in the Frontiers in Microbiology, researchers assessed the impact of diet or macronutrient consumption on the function and structure of gut microbiota.
Shifting ingestive behavior is crucial for animals to adjust to environmental change. Studies have recognized that changes in animal feeding habits lead to gut microbiota structure alterations. However, further research is required to understand the alterations incident in the structure as well as the function of the gut microbiota that occur in response to alterations in nutrient consumption or food types.
About the study
In the present study, researchers explored how animal feeding techniques influence nutrient consumption and further affect the content and digestive function of the gut microbiota.
The study observation site was in the Guanyin Mountain National Natural Reserve in the Qinling Mountains, northwest of Fuping County, Shaanxi Province, China. During a year, this area experiences conventional and four different seasons. According to climate, the seasons are as follows: Spring between March and May, Summer between June and August, Autumn between September and November, and Winter between December and February.
The team compiled feeding information for the four seasonal groupings. For data collection, a month with typical phenological characteristics for each season: March for Spring, June for Summer, October for Autumn, and December for Winter.
All of the 78 golden snub-nosed monkeys in the study group were accustomed to the presence of researchers. The team identified both adult and young individuals in the study cohort. Due to the necessity for quantitative observational data, the natural feeding area of the study animals was restricted. The team provided five kilograms of maize twice daily at 10 am and 3 pm as supplemental nourishment for the group. The feed grounds were evenly strewn with corn kernels.
The team randomly selected one individual per day and observed the subject animal continuously from sunrise to dusk to record data related to its feeding pattern. Furthermore, the type of food, quantity, preset units, and feeding duration were recorded. After the subject had finished eating, food samples were gathered from the leftovers.
Food samples were collected using conventional procedures, their nutritional content was assessed, and their energy content was computed. The lipid, starch, water-soluble carbohydrate (WSC), acid detergent fiber (ADF), neutral detergent fiber (NDF), acid detergent lignin (ADL), ash content of each food, and available protein (AP) were evaluated.
Results
Data related to 96 days of feeding across four months were obtained from the target population. It was discovered that the normal diet of golden snub-nosed monkeys in the wild comprised 24 plant species from 16 families. A total of six plant parts, including branches, buds, seeds, barks, leaves, and stems, were consumed by the subjects.
Throughout the year, wild snub-nosed monkeys eat 33.43% of bark, 3.09% of seed, 1.33% of bud, 3.25% of brunch, 0.17% of the stem, and 58.72% of the leaf. Nonetheless, there were significant variations in the number of plant materials consumed over the four seasons. Herbaceous stems were harvested only in tiny quantities in the Spring. Mostly, seeds were harvested in the Spring and fall. The harvesting of leaves occurred throughout the year. Throughout fall and Winter, when leaves become sparse, especially in Winter, barks, buds, and brunches were the principal sources of nutrition.
The species composition was evaluated to explore seasonal changes in gut microbiota in greater depth. Species annotation revealed that most OTUs could be assigned taxonomically at the phylum and order levels, but assignments reduced dramatically at the genus level.
The top 10 phyla out of 38 phyla recognized dominant phyla, including Bacteroidetes, Firmicutes, Spirochaetes, Proteobacteria, Tenericutes, Planctomycetes, Verrucomicrobia, Epsilonbacteriaeota, Euryarchaeota, and Fibrobacteres comprised 99% of the total abundance ratio. They comprised the majority of the golden snub-nosed monkeys’ gut microbiome.
Three hundred ninety-five metabolic pathways were found based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database’s function prediction. Gut microbes were primarily engaged in the metabolism of nucleotides, carbohydrates, glycans and their production, amino acids, terpenoids, lipids, cofactors, polyketides, and vitamins.
Moreover, some annotated functions pertaining to macronutrients exhibited relatively high abundance, including glycolysis/gluconeogenesis, pyruvate metabolism, sucrose and starch metabolism, glycerolipid metabolism, fatty acid synthesis in lipid metabolism, and pentose phosphate pathway in glycerophospholipid metabolism and carbohydrate metabolism.
Conclusion
The study findings showed a considerable seasonal change in the food consumption and nutritional intake of golden snub-nosed monkeys, with three macronutrients being higher in Autumn and Summer and lower in Winter and Spring. Seasonal dietary changes are the primary source of seasonal shifts in gut microbiota. The results indicated that bacteria in the gut compensate for inadequate macronutrient intake through microbial metabolic functions.