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"Nielsen, Dennis S."
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A polyphenol-enriched diet and Ascaris suum infection modulate mucosal immune responses and gut microbiota composition in pigs
by
Williams, Andrew R.
,
Thamsborg, Stig M.
,
Nielsen, Dennis S.
in
Animal sciences
,
Animals
,
Anthelmintic agents
2017
Polyphenols are a class of bioactive plant secondary metabolites that are thought to have beneficial effects on gut health, such as modulation of mucosal immune and inflammatory responses and regulation of parasite burdens. Here, we examined the interactions between a polyphenol-rich diet supplement and infection with the enteric nematode Ascaris suum in pigs. Pigs were fed either a basal diet or the same diet supplemented with grape pomace (GP), an industrial by-product rich in polyphenols such as oligomeric proanthocyanidins. Half of the animals in each group were then inoculated with A. suum for 14 days to assess parasite establishment, acquisition of local and systemic immune responses and effects on the gut microbiome. Despite in vitro anthelmintic activity of GP-extracts, numbers of parasite larvae in the intestine were not altered by GP-supplementation. However, the bioactive diet significantly increased numbers of eosinophils induced by A. suum infection in the duodenum, jejunum and ileum, and modulated gene expression in the jejunal mucosa of infected pigs. Both GP-supplementation and A. suum infection induced significant and apparently similar changes in the composition of the prokaryotic gut microbiota, and both also decreased concentrations of isobutyric and isovaleric acid (branched-chain short chain fatty acids) in the colon. Our results demonstrate that while a polyphenol-enriched diet in pigs may not directly influence A. suum establishment, it significantly modulates the subsequent host response to helminth infection. Our results suggest an influence of diet on immune function which may potentially be exploited to enhance immunity to helminths.
Journal Article
A prebiotic intervention study in children with autism spectrum disorders (ASDs)
by
Costabile, Adele
,
Hansen, Lars H.
,
Giallourou, Natasa
in
Autism
,
Autism Spectrum Disorder - diet therapy
,
Autism Spectrum Disorder - microbiology
2018
Background
Different dietary approaches, such as gluten and casein free diets, or the use of probiotics and prebiotics have been suggested in autistic spectrum disorders in order to reduce gastrointestinal (GI) disturbances. GI symptoms are of particular interest in this population due to prevalence and correlation with the severity of behavioural traits. Nowadays, there is lack of strong evidence about the effect of dietary interventions on these problems, particularly prebiotics. Therefore, we assessed the impact of exclusion diets and a 6-week Bimuno® galactooligosaccharide (B-GOS®) prebiotic intervention in 30 autistic children.
Results
The results showed that children on exclusion diets reported significantly lower scores of abdominal pain and bowel movement, as well as lower abundance of
Bifidobacterium
spp. and Veillonellaceae family, but higher presence of
Faecalibacterium prausnitzii
and
Bacteroides
spp. In addition, significant correlations were found between bacterial populations and faecal amino acids in this group, compared to children following an unrestricted diet. Following B-GOS® intervention, we observed improvements in anti-social behaviour, significant increase of Lachnospiraceae family, and significant changes in faecal and urine metabolites.
Conclusions
To our knowledge, this is the first study where the effect of exclusion diets and prebiotics has been evaluated in autism, showing potential beneficial effects. A combined dietary approach resulted in significant changes in gut microbiota composition and metabolism suggesting that multiple interventions might be more relevant for the improvement of these aspects as well as psychological traits.
Trial registration
NCT02720900
; registered in November 2015.
Journal Article
Quantitatively Different, yet Qualitatively Alike: A Meta-Analysis of the Mouse Core Gut Microbiome with a View towards the Human Gut Microbiome
2013
A number of human diseases such as obesity and diabetes are associated with changes or imbalances in the gut microbiota (GM). Laboratory mice are commonly used as experimental models for such disorders. The introduction and dynamic development of next generation sequencing techniques have enabled detailed mapping of the GM of both humans and animal models. Nevertheless there is still a significant knowledge gap regarding the human and mouse common GM core and thus the applicability of the latter as an animal model. The aim of the present study was to identify inter- and intra-individual differences and similarities between the GM composition of particular mouse strains and humans.
A total of 1509428 high quality tag-encoded partial 16S rRNA gene sequences determined using 454/FLX Titanium (Roche) pyro-sequencing reflecting the GM composition of 32 human samples from 16 individuals and 88 mouse samples from three laboratory mouse strains commonly used in diabetes research were analyzed using Principal Coordinate Analysis (PCoA), nonparametric multivariate analysis of similarity (ANOSIM) and alpha diversity measures. A reliable cutoff threshold for low abundant taxa estimated on the basis of the present study is recommended for similar trials.
Distinctive quantitative differences in the relative abundance of most taxonomic groups between the examined categories were found. All investigated mouse strains clustered separately, but with a range of shared features when compared to the human GM. However, both mouse fecal, caecal and human fecal samples shared to a large extent not only representatives of the same phyla, but also a substantial fraction of common genera, where the number of shared genera increased with sequencing depth. In conclusion, the GM of mice and humans is quantitatively different (in terms of abundance of specific phyla and species) but share a large qualitatively similar core.
Journal Article
Virulent coliphages in 1-year-old children fecal samples are fewer, but more infectious than temperate coliphages
2020
Bacteriophages constitute an important part of the human gut microbiota, but their impact on this community is largely unknown. We cultivated temperate phages produced by 900 E. coli strains isolated from 648 fecal samples of children 1-year-old. Next, we isolated coliphages directly from the viral fraction of the same fecal samples. We found that 63% of strains hosted phages, while 24% of the viromes contained phages targeting E. coli. 150 of these phages, half recovered from strain supernatants, half from virome (73% temperate and 27% virulent) were tested for their host range on 75 E. coli strains isolated from the same cohort. Temperate phages barely infected the gut strains, whereas virulent phages killed up to 68% of them. We conclude that in fecal samples from children, temperate coliphages dominate, while virulent ones have greater infectivity and broader host range, likely playing a role in gut microbiota dynamics.
Journal Article
Linking gut microbiota rhythmicity to circadian maturation in infants
by
Schoch, Sarah F.
,
Mühlematter, Christophe
,
Castro-Mejía, Josue L.
in
692/308/3187
,
692/53/2423
,
Actimetry
2025
The human gut microbiota undergoes daily fluctuations, yet its interaction with sleep-wake patterns during infancy remains largely uncharted. This study aims to elucidate the relationship between gut microbiota rhythmicity and the development of sleep patterns in infants over the first year of life. We continuously monitored 162 healthy infants across multiple days at 3, 6, and 12 months of age using ankle actigraphy and 24-hour diaries. The Circadian Function Index (CFI) was computed as a proxy for sleep-wake rhythm maturation. Stool samples were collected to profile gut microbiota taxa composition via 16 S rRNA gene amplicon sequencing, and microbial oscillations were assessed through sine and cosine fitting to detect 24-hour patterns. Our findings revealed that the relative abundance of bacterial taxa exhibited rhythmic patterns, with 26 zOTUs (1.74%) following a sine pattern and 100 zOTUs (6.69%) displaying cosine rhythmicity. Cosine rhythmicity became more pronounced with age, showing strong maturation: 7 zOTUs at 3 months, 2 zOTUs at 6 months, and 86 zOTUs at 12 months. Notably, 105 zOTUs (7.02%) were associated with CFI, demonstrating a significant relationship between gut microbiota rhythms and sleep development. Among these, 27 zOTUs with sine dynamics and 96 zOTUs with cosine dynamics were linked to CFI, with this association strengthening as infants aged. These results highlight the increasing synchronization between gut microbiota rhythmicity and sleep-wake cycles during infancy, pointing to a critical window for potential health interventions. This novel observation, previously reported in rodents and adults, underscores the role of gut microbiota in early human development, offering new avenues for enhancing developmental outcomes through targeted interventions.
Journal Article
Infant gut anellovirus composition associates with early life factors and childhood atopic disease
2025
Anelloviruses are single-stranded circular DNA viruses that infect eukaryotic cells. They are acquired in infancy and can be found in most body compartments. The
Anelloviridae
family is highly prevalent and genetically diverse, but factors shaping the composition and the relationship with disease remain elusive. Here, we characterise faecal viromes of 647 one-year-old children from the deeply phenotyped Copenhagen Prospective Studies on Asthma in Childhood
2010
(COPSAC
2010
) mother-child cohort. In this study, 111 unique anellovirus species are identified and reveal immense prevalence and individual variability. The anellovirus and bacteriophage compositions are slightly correlated, while no correlation is observed with the bacterial composition. Early-life exposures such as attending day care and having older siblings are associated with a reduced anellovirus abundance and diversity, and influence the anellovirus composition. Additionally, genetic secretors of the FUT2 enzyme have a higher anellovirus abundance compared to non-secretors. Minor associations are observed between anelloviruses and later allergic rhinitis, but no associations are found for concurrent acute infections or the development of other atopic traits. Our findings indicate that anelloviruses are a commensal component of all infants’ faecal virome, and further investigations into how immune-training factors influence their composition longitudinally are pertinent.
Here, the authors characterize the gut virome of 647 one-year-old children in the COPSAC2010 cohort, finding that anelloviruses are highly prevalent and associated with daycare attendance, gestational age, and FUT2 secretor status.
Journal Article
Gut microbiota patterns associated with duration of diarrhea in children under five years of age in Ethiopia
2024
Diarrhea claims >500,000 lives annually among children under five years of age in low- and middle-income countries. Mortality due to acute diarrhea (<7 days’ duration) is decreasing, but prolonged (7-13 days) and persistent (≥14 days of duration) diarrhea remains a massive challenge. Here, we use a case-control study to decipher if fecal gut microbiota compositional differences between Ethiopian children with acute (n=554) or prolonged/persistent (n=95) diarrhea and frequency-matched non-diarrheal controls (n=663) are linked to diarrheal etiology. We show that diarrhea cases are associated with lower bacterial diversity and enriched in
Escherichia
spp.,
Campylobacter
spp., and
Streptococcus
spp. Further, diarrhea cases are depleted in gut commensals such as
Prevotella copri
,
Faecalibacterium prausnitzii
, and
Dialister succinatiphilus
, with depletion being most pronounced in prolonged/persistent cases, suggesting that prolonged duration of diarrhea is accompanied by depletion of gut commensals and that re-establishing these via e.g., microbiota-directed food supplements offer a potential treatment strategy.
Here, the authors profile the gut microbiome of Ethiopian children suffering from acute and prolonged diarrhea, showing the latter group to exhibit a higher degree of microbial imbalance, characterized by a reduction of gut commensals and an enrichment of potential pathogens.
Journal Article
Microbiota in foods from Inuit traditional hunting
by
Paulová, Petronela
,
Hauptmann, Aviaja L.
,
Hansen, Lars Hestbjerg
in
Animal-based foods
,
Animals
,
Animals, Wild - microbiology
2020
The foods we eat contain microorganisms that we ingest alongside the food. Industrialized food systems offer great advantages from a safety point of view, but have also been accused of depleting the diversity of the human microbiota with negative implications for human health. In contrast, artisanal traditional foods are potential sources of a diverse food microbiota. Traditional foods of the Greenlandic Inuit are comprised of animal-sourced foods prepared in the natural environment and are often consumed raw. These foods, some of which are on the verge of extinction, have not previously been microbiologically characterized. We mapped the microbiota of foods stemming from traditional Inuit land-based hunting activities. The foods included in the current study are dried muskox and caribou meat, caribou rumen and intestinal content as well as larval parasites from caribou hides, all traditional Inuit foods. This study shows that traditional drying methods are efficient for limiting microbial growth through desiccation. The results also show the rumen content of the caribou to be a highly diverse source of microbes with potential for degradation of plants. Finally, a number of parasites were shown to be included in the biodiversity of the assessed traditional foods. Taken together, the results map out a diverse source of ingested microbes and parasites that originate from the natural environment. These results have implications for understanding the nature-sourced traditional Inuit diet, which is in contrast to current day diet recommendations as well as modern industrialized food systems.
Journal Article
Not simply a matter of parents—Infants’ sleep-wake patterns are associated with their regularity of eating
by
Wright, Kenneth P.
,
Mühlematter, Christophe
,
Nielsen, Dennis S.
in
Adult
,
Antibiotics
,
Babies
2023
In adults there are indications that regular eating patterns are related to better sleep quality. During early development, sleep and eating habits experience major maturational transitions. Further, the bacterial landscape of the gut microbiota undergoes a rapid increase in complexity. Yet little is known about the association between sleep, eating patterns and the gut microbiota. We first hypothesized that higher eating regularity is associated with more mature sleep patterns, and second, that this association is mediated by the maturational status of the gut microbiota. To test this hypothesis, we performed a longitudinal study in 162 infants to assess actigraphy, diaries of sleep and eating times, and stool microbiota composition at ages 3, 6 and 12 months. To comprehensively capture infants’ habitual sleep-wake patterns, 5 sleep composites that characterize infants’ sleep habits across multiple days in their home environment were computed. To assess timing of eating habits, we developed an Eating Regularity Index (ERI). Gut microbial composition was assessed by 16S rRNA gene amplicon sequencing, and its maturation was assessed based on alpha diversity, bacterial maturation index, and enterotype. First, our results demonstrate that increased eating regularity (higher ERI) in infants is associated with less time spent awake during the night (sleep fragmentation) and more regular sleep patterns. Second, the associations of ERI with sleep evolve with age. Third, the link between infant sleep and ERI remains significant when controlling for parents’ subjectively rated importance of structuring their infant’s eating and sleeping times. Finally, the gut microbial maturational markers did not account for the link between infant’s sleep patterns and ERI. Thus, infants who eat more regularly have more mature sleep patterns, which is independent of the maturational status of their gut microbiota. Interventions targeting infant eating rhythm thus constitute a simple, ready-to-use anchor to improve sleep quality.
Journal Article
Effect of gluten-free diet and antibiotics on murine gut microbiota and immune response to tetanus vaccination
by
Hansen, Lars H.
,
Skov, Søren
,
Kihl, Pernille
in
Animal sciences
,
Animals
,
Anti-Bacterial Agents - pharmacology
2022
The purpose of this study was to compare the effect of a gluten-free diet and/or antibiotics on tetanus vaccine induced immunoglobulin G titers and immune cell levels in BALB/c mice. The gluten-free diet was associated with a reduced anti-tetanus IgG response, and it increased the relative abundance of the anti-inflammatory Bifidobacterium significantly in some of the mice. Antibiotics also led to gut microbiota changes and lower initial vaccine titer. After a second vaccination, neither gluten-free diet nor antibiotics reduced the titers. In the spleen, the gluten-free diet significantly increased regulatory T cell (T reg ) fractions, CD4 + T cell activation, and tolerogenic dendritic cell fractions and activation, which extend the downregulating effect of the T reg . Therefore, the systemic effect of the gluten-free diet seems mainly tolerogenic. Antibiotics reduced the fractions of CD4 + T and B cells in the mesenteric lymph nodes. These results suggest that vaccine response in mice is under influence of their diet, the gut microbiota and the interplay between them. However, a gluten-free diet seems to work through mechanisms different from those induced by antibiotics. Therefore, diet should be considered when testing vaccines in mice and developing vaccines for humans.
Journal Article