Publications by authors named "Dennis S Nielsen"

102 Publications

Effect of gluten-free diet and antibiotics on murine gut microbiota and immune response to tetanus vaccination.

PLoS One 2022 13;17(4):e0266719. Epub 2022 Apr 13.

Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.

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 (Treg) fractions, CD4+ T cell activation, and tolerogenic dendritic cell fractions and activation, which extend the downregulating effect of the Treg. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266719PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007335PMC
April 2022

Dietary proanthocyanidins promote localized antioxidant responses in porcine pulmonary and gastrointestinal tissues during Ascaris suum-induced type 2 inflammation.

FASEB J 2022 04;36(4):e22256

Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.

Proanthocyanidins (PAC) are dietary polyphenols with putative anti-inflammatory and immunomodulatory effects. However, whether dietary PAC can regulate type-2 immune function and inflammation at mucosal surfaces remains unclear. Here, we investigated if diets supplemented with purified PAC modulated pulmonary and intestinal mucosal immune responses during infection with the helminth parasite Ascaris suum in pigs. A. suum infection induced a type-2 biased immune response in lung and intestinal tissues, characterized by pulmonary granulocytosis, increased Th2/Th1 T cell ratios in tracheal-bronchial lymph nodes, intestinal eosinophilia, and modulation of genes involved in mucosal barrier function and immunity. Whilst PAC had only minor effects on pulmonary immune responses, RNA-sequencing of intestinal tissues revealed that dietary PAC significantly enhanced transcriptional responses related to immune function and antioxidant responses in the gut of both naïve and A. suum-infected animals. A. suum infection and dietary PAC induced distinct changes in gut microbiota composition, primarily in the jejunum and colon, respectively. Notably, PAC consumption substantially increased the abundance of Limosilactobacillus reuteri. In vitro experiments with porcine macrophages and intestinal epithelial cells supported a role for both PAC polymers and PAC-derived microbial metabolites in regulating oxidative stress responses in host tissues. Thus, dietary PAC may have distinct beneficial effects on intestinal health during infection with mucosal pathogens, while having a limited activity to modulate naturally-induced type-2 pulmonary inflammation. Our results shed further light on the mechanisms underlying the health-promoting properties of PAC-rich foods, and may aid in the design of novel dietary supplements to regulate mucosal inflammatory responses in the gastrointestinal tract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202101603RRDOI Listing
April 2022

Effects of Calcium Source, Inulin, and Lactose on Gut-Bone Associations in an Ovarierectomized Rat Model.

Mol Nutr Food Res 2022 04 17;66(8):e2100883. Epub 2022 Feb 17.

Department of Food Science, Aarhus University, Agro Food Park 48, Aarhus N, DK-8200, Denmark.

Scope: Osteoporosis poses a health challenge especially for postmenopausal women. This study aims to explore nutritional strategies to counteract bone demineralization in ovarierectomized (OVX) rats.

Methods And Results: OVX rats (n = 49) are fed with one of six different diets, where two different calcium sources (dairy calcium or calcium carbonate) are provided alone or in combination with either inulin (5%) or lactose (0.5%). In addition, a calcium-deficient diet is included. Calcium supplementation increases intestinal concentrations of short-chain fatty acids (SCFAs) and the abundance of fecal Acinetobacter and Propionibacterium. Accompanied with these effects, rats fed with calcium-fortified diets have higher bone mineral density, bone mineral content and femur mechanical strength, lower serum levels of bone markers, and lower expression of calcium absorption-related genes (transient receptor potential vanilloid type 6 (TRPV6), calcium-binding protein (CaBP) compared with control. Inulin supplementation results in a markedly increased production of intestinal SCFAs, a decreased intestinal pH, an increased abundance of Allobaculum and Bifidobacterium, and an increased expression of Trpv6. Inulin and lactose show beneficial effects on spine bone.

Conclusion: Calcium modulates gut microbiome composition and function. A pronounced effect of inulin on metabolic activity in the gastrointestinal tract is evident, and lactose supplementation decreases jejunal pH that might be associated with slightly enhanced bone mineralization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mnfr.202100883DOI Listing
April 2022

Gluten-free diet reduces autoimmune diabetes mellitus in mice across multiple generations in a microbiota-independent manner.

J Autoimmun 2022 02 31;127:102795. Epub 2022 Jan 31.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Experimental and clinical data suggest that a gluten-free diet attenuates the development of type 1 diabetes. A gluten-free diet changes the gut microbiota composition, and such microbial changes are expected to reduce the autoimmune responses. However, in experiments with laboratory mice, a gluten-free diet changes the gut microbiota differently under varying experimental settings, questioning the specific role of the gut microbes. Here we show that a maternal gluten-free diet until weaning of their pups, delayed type 1 diabetes in both dams (parent generation) and offspring (F1 generation) of untreated non-obese diabetic (NOD) mice and in mice treated with a full cocktail of antibiotics that eradicates most of the existing microbiota. Breeding a second (F2) generation of NOD mice, never exposed to the gluten-free diet or the associated microbial changes, also demonstrated a preventative effect on type 1 diabetes even though their parents (the F1 generation) had only been on a gluten-free diet very early in life. Collectively, the experimental data, thus, points towards microbiota-independent dietary protection. Furthermore, both the perinatal gluten-free diet and antibiotic treatment reduced inflammation in the salivary glands and improved glucose challenged beta cell function in the F1 offspring. However, in contrast to the autoimmune response in the pancreas, those changes appeared to be microbiota dependent, as they were missing in the antibiotic treated mice, and do, therefore, not seem to be related to the preventative effect on type 1 diabetes. Interestingly, adoptive transfer of splenocytes from gluten-free fed mice protected NOD.SCID mice from developing diabetes, demonstrating that the anti-diabetic effect of a gluten-free diet was based on early life changes in the evolving immune system. In particular, genes involved in regulation of lymphocyte activation, proliferation, and cell adhesion were highly expressed in the spleen in gluten-free fed mice at weaning compared to control fed mice of the F1 generation, which suggested that gluten promotes autoimmunity by inhibiting immune regulation, though the involvement of the specific genes needs further investigation. In conclusion, gluten-free diet reduces autoimmune inflammation in salivary glands and pancreas in NOD mice in a microbiota-dependent and -independent manner respectively, and has preventative effect on type 1 diabetes by modulating the systemic immune system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaut.2022.102795DOI Listing
February 2022

Parasite-Probiotic Interactions in the Gut: sp. and Regulate Type-2 Inflammatory Responses and Modify the Gut Microbiota of Pigs During Helminth Infection.

Front Immunol 2021 5;12:793260. Epub 2022 Jan 5.

Department of Veterinary and Animal Sciences, University of Copenhagen, Faculty of Health and Medical Sciences, Frederiksberg, Denmark.

Dietary probiotics may enhance gut health by directly competing with pathogenic agents and through immunostimulatory effects. These properties are recognized in the context of bacterial and viral pathogens, but less is known about interactions with eukaryotic pathogens such as parasitic worms (helminths). In this study we investigated whether two probiotic mixtures (comprised of , and [BBE], or LGG and subspecies Bb12 [LB]) could modulate helminth infection kinetics as well as the gut microbiome and intestinal immune responses in pigs infected with the nodular worm . We observed that neither probiotic mixture influenced helminth infection levels. BBE, and to a lesser extent LB, changed the alpha- and beta-diversity indices of the colon and fecal microbiota, notably including an enrichment of fecal spp. by BBE. However, these effects were muted by concurrent infection. BBE (but not LB) significantly attenuated the -induced upregulation of genes involved in type-2 inflammation and restored normal lymphocyte ratios in the ileo-caecal lymph nodes that were altered by infection. Moreover, inflammatory cytokine release from blood mononuclear cells and intestinal lymphocytes was diminished by BBE. Collectively, our data suggest that selected probiotic mixtures can play a role in maintaining immune homeostasis during type 2-biased inflammation. In addition, potentially beneficial changes in the microbiome induced by dietary probiotics may be counteracted by helminths, highlighting the complex inter-relationships that potentially exist between probiotic bacteria and intestinal parasites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.793260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766631PMC
February 2022

Human Blood Lipoprotein Predictions from H NMR Spectra: Protocol, Model Performances, and Cage of Covariance.

Anal Chem 2022 01 22;94(2):628-636. Epub 2021 Dec 22.

Department of Food Science, University of Copenhagen, Rolighedsvej 26, DK-1958 Frederiksberg C, Denmark.

Lipoprotein subfractions are biomarkers for the early diagnosis of cardiovascular diseases. The reference method, ultracentrifugation, for measuring lipoproteins is time-consuming, and there is a need to develop a rapid method for cohort screenings. This study presents partial least-squares regression models developed using H nuclear magnetic resonance (NMR) spectra and concentrations of lipoproteins as measured by ultracentrifugation on 316 healthy Danes. This study explores, for the first time, different regions of the H NMR spectrum representing signals of molecules in lipoprotein particles and different lipid species to develop parsimonious, reliable, and optimal prediction models. A total of 65 lipoprotein main and subfractions were predictable with high accuracy, of >0.6, using an optimal spectral region (1.4-0.6 ppm) containing methylene and methyl signals from lipids. The models were subsequently tested on an independent cohort of 290 healthy Swedes with predicted and reference values matching by up to 85-95%. In addition, an open software tool was developed to predict lipoproteins concentrations in human blood from standardized H NMR spectral recordings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.1c01654DOI Listing
January 2022

The phytonutrient cinnamaldehyde limits intestinal inflammation and enteric parasite infection.

J Nutr Biochem 2022 02 14;100:108887. Epub 2021 Oct 14.

Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark. Electronic address:

Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA in mice significantly down-regulates transcriptional pathways connected to inflammation in the small intestine, and alters T-cell populations in mesenteric lymph nodes. During infection with the enteric helminth Heligomosomoides polygyrus, CA treatment attenuated infection-induced changes in biological pathways connected to cell cycle and mitotic activity, and tended to reduce worm burdens. Mechanistically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Collectively, our results show that CA down-regulates inflammatory pathways in the intestinal mucosa and can limit the pathological response to enteric infection. These properties appear to be largely independent of the gut microbiota, and instead connected to the ability of CA to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jnutbio.2021.108887DOI Listing
February 2022

Targeted Screening of Lactic Acid Bacteria With Antibacterial Activity Toward Clonal Complex Type 1 Associated With Atopic Dermatitis.

Front Microbiol 2021 17;12:733847. Epub 2021 Sep 17.

Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by an epidermal barrier impairment, as well as a Th2/Th22-skewed immune response, both favoring skin colonization with . Colonization is strongly related to severity of the disease, and a reduction of has been found to alleviate symptoms. Lactic acid bacteria (LAB) produce antimicrobial compounds such as organic acids and bacteriocins and are widely used as probiotics. The aim of this study was to isolate LAB and screen for antibacterial effect specifically toward clonal complex type 1. A total of 680 LAB were isolated from fermented vegetables and swab samples from healthy volunteers (vaginal, stool and skin). Screening for antibacterial activity toward , narrowed the field of isolates down to four LAB strains with high antibacterial activity. The activity varied according to the specific LAB strain and the origin of the strain. The results suggested different modes of action, including co-aggregation, expression of bacteriocins and production of specific organic acids. However, the ability to acidify the surroundings appeared as the main effect behind inhibition of Broth microdilution assays showed a significant reduction of growth when using down to 10% cell free supernatant (CFS). Our results underline the use of specific living LAB or their CFS as potential future treatment strategies to reduce colonization of AD skin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.733847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486014PMC
September 2021

Effect of processing on digestibility (IVPD) of food proteins.

Crit Rev Food Sci Nutr 2021 Sep 30:1-50. Epub 2021 Sep 30.

Research Institute of Meat and Meat Products (IproCar), University of Extremadura, Cáceres, Spain.

Proteins are important macronutrients for the human body to grow and function throughout life. Although proteins are found in most foods, their very dissimilar digestibility must be taking into consideration when addressing the nutritional composition of a diet. This review presents a comprehensive summary of the digestibility of proteins from plants, milk, muscle, and egg. It is evident from this work that protein digestibility greatly varies among foods, this variability being dependent not only upon the protein source, but also the food matrix and the molecular interactions between proteins and other food components (food formulation), as well as the conditions during food processing and storage. Different approaches have been applied to assess protein digestibility (IVPD), varying in both the enzyme assay and quantification method used. In general, animal proteins tend to show higher IVPD. Harsh technological treatments tend to reduce IVPD, except for plant proteins, in which thermal degradation of anti-nutritional compounds results in improved IVPD. However, in order to improve the current knowledge about protein digestibility there is a vital need for understanding dependency on a protein source, molecular interaction, processing and formulation and relationships between. Such knowledge can be used to develop new food products with enhanced protein bioaccessibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10408398.2021.1980763DOI Listing
September 2021

Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response in Apoe knockout mice with an unhealthy lipoprotein distribution.

Sci Rep 2021 08 12;11(1):16423. Epub 2021 Aug 12.

Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.

This study explores if unhealthy lipoprotein distribution (LPD) impairs the anabolic and amino acid sensing responses to whey-protein feeding. Thus, if impairment of such anabolic response to protein consumption is seen by the LPD this may negatively affect the skeletal muscle mass. Muscle protein synthesis (MPS) was measured by puromycin labeling in Apolipoprotein E knockout (Apoe KO), characterized by an unhealthy LPD, and wild type mice post-absorptive at 10 and 20 weeks, and post-prandial after whey-protein feeding at 20 weeks. Hypertrophy signaling and amino acid sensing mechanisms were studied and gut microbiome diversity explored. Surprisingly, whey-protein feeding did not affect MPS. p-mTOR and p-4E-BP1 was increased 2 h after whey-protein feeding in both genotypes, but with general lower levels in Apoe KO compared to wild type. At 20 weeks of age, Apoe KO had a greater mRNA-expression for SNAT2, CD98, ATF4 and GCN2 compared to wild type. These responses were not associated with gut microbiota compositional differences. Regardless of LPD status, MPS was similar in Apoe KO and wild type. Surprisingly, whey-protein did not stimulate MPS. However, Apoe KO had lower levels of hypertrophy signaling, was amino acid deprived, and had impaired amino acid sensing mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-96000-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360952PMC
August 2021

The Gut Microbiome and Abiotic Factors as Potential Determinants of Postprandial Glucose Responses: A Single-Arm Meal Study.

Front Nutr 2020 14;7:594850. Epub 2021 Jan 14.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark.

The gut microbiome has combined with other person-specific information, such as blood parameters, dietary habits, anthropometrics, and physical activity been found to predict personalized postprandial glucose responses (PPGRs) to various foods. Yet, the contributions of specific microbiome taxa, measures of fermentation, and abiotic factors in the colon to glycemic control remain elusive. We tested whether PPGRs 60 min after a standardized breakfast was associated with gut microbial α-diversity (primary outcome) and explored whether postprandial responses of glucose and insulin were associated with specific microbiome taxa, colonic fermentation as reflected by fecal short-chain fatty acids (SCFAs), and breath hydrogen and methane exhalation, as well as abiotic factors including fecal pH, fecal water content, fecal energy density, intestinal transit time (ITT), and stool consistency. A single-arm meal trial was conducted. A total of 31 healthy (24 female and seven male) subjects consumed a standardized evening meal and a subsequent standardized breakfast (1,499 kJ) where blood was collected for analysis of postprandial glucose and insulin responses. PPGRs to the same breakfast varied across the healthy subjects. The largest inter-individual variability in PPGRs was observed 60 min after the meal but was not associated with gut microbial α-diversity. In addition, no significant associations were observed between postprandial responses and specific taxa of the gut microbiome, measures of colonic fermentation, ITT, or other abiotic factors. However, fasting glucose concentrations were negatively associated with ITT, and fasting insulin was positively associated with fasting breath hydrogen. In conclusion, the gut microbiome, measures of colonic fermentation, and abiotic factors were not shown to be significantly associated with variability in postprandial responses, suggesting that contributions of the gut microbiome, colonic fermentation, and abiotic factors to PPGRs may be subtle in healthy adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2020.594850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874175PMC
January 2021

The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial.

Am J Clin Nutr 2021 04;113(4):790-800

Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark.

Background: Protein supplementation alone or combined with resistance training has been proposed to be effective in counteracting age-related losses of muscle mass and strength.

Objectives: To investigate the effect of protein supplementation alone or combined with light-intensity or heavy-load resistance exercise on muscle size, strength, and function in older adults.

Methods: In a 1-y randomized controlled trial, 208 healthy older adults (>65 y) were randomly assigned to 1 of 5 interventions: 1) carbohydrate supplementation (CARB); 2) collagen protein supplementation (COLL); 3) whey protein supplementation (WHEY); 4) light-intensity resistance training 3-5 times/wk with whey protein supplementation (LITW); and 5) heavy resistance training 3 times weekly with whey protein supplementation (HRTW). Protein supplements contained 20 g protein + 10 g carbohydrate, whereas CARB contained 30 g of carbohydrates. All intervention groups received the supplement twice daily. The primary outcome was change in the quadriceps cross-sectional area (qCSA). Secondary outcomes included measures of lower extremity strength and power, functional capabilities, and body composition.

Results: There were 184 participants who completed the study. COLL and WHEY did not affect any measured parameter compared to CARB. Compared to WHEY, HRTW improved the qCSA size (between-group difference, +1.68 cm2; 95% CI, +0.41 to +2.95 cm2; P = 0.03), as well as dynamic (+18.4 Nm; 95% CI, +10.1 to +26.6 Nm; P < 10-4) and isometric knee extensor strength (+23.9 Nm; 95% CI, +14.2 to +33.6 Nm; P < 10-5). LITW did not improve the qCSA size, but increased dynamic knee extensor strength compared to WHEY (+13.7 Nm; 95% CI, +5.3 and +22.1 Nm; P = 0.01).

Conclusions: Recommending protein supplementation as a stand-alone intervention for healthy older individuals seems ineffective in improving muscle mass and strength. Only HRTW was effective in both preserving muscle mass and increasing strength. Thus, we recommend that future studies investigate strategies to increase long-term compliance to heavy resistance exercise in healthy older adults. This trial was registered at clinicaltrials.gov as NCT02034760.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqaa372DOI Listing
April 2021

Emerging interactions between diet, gastrointestinal helminth infection, and the gut microbiota in livestock.

BMC Vet Res 2021 Jan 29;17(1):62. Epub 2021 Jan 29.

Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark.

Increasing evidence suggests that nutritional manipulation of the commensal gut microbiota (GM) may play a key role in maintaining animal health and production in an era of reduced antimicrobial usage. Gastrointestinal helminth infections impose a considerable burden on animal performance, and recent studies suggest that infection may substantially alter the composition and function of the GM. Here, we discuss the potential interactions between different bioactive dietary components (prebiotics, probiotics and phytonutrients) and helminth infection on the GM in livestock. A number of recent studies suggest that host diet can strongly influence the nature of the helminth-GM interaction. Nutritional manipulation of the GM may thus impact helminth infection, and conversely infection may also influence how the GM responds to dietary interventions. Moreover, a dynamic interaction exists between helminths, the GM, intestinal immune responses, and inflammation. Deciphering the mechanisms underlying the diet-GM-helminth axis will likely inform future helminth control strategies, as well as having implications for how health-promoting feed additives, such as probiotics, can play a role in sustainable animal production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12917-021-02752-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845040PMC
January 2021

Thymus size and its correlates among children admitted with severe acute malnutrition: a cross-sectional study in Uganda.

BMC Pediatr 2021 01 4;21(1). Epub 2021 Jan 4.

Department of Nutrition, Exercise and Sports, University of Copenhagen, DK-1958, Frederiksberg C, Denmark.

Background: Malnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM.

Methods: This cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM.

Results: Among 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm, p<0.001) when controlled for age. Thymus size positively correlated with current breastfeeding (0.14, 95% CI 0.01, 0.26), anthropometric measurements at admission (weight, length, mid-upper-arm circumference, weight-for-height Z scores and length-for-age Z scores) and suspected tuberculosis (0.12, 95% CI 0.01; 0.22). Thymus size negatively correlated with > 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01).

Conclusion: The thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-020-02457-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780382PMC
January 2021

Dietary prebiotics promote intestinal Prevotella in association with a low-responding phenotype in a murine oxazolone-induced model of atopic dermatitis.

Sci Rep 2020 12 3;10(1):21204. Epub 2020 Dec 3.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Atopic dermatitis is a chronic eczema commonly observed among children in Western countries. The gut microbiota is a significant factor in the pathogenesis, and ways to promote intestinal colonizers with anti-inflammatory capabilities are therefore favorable. The present study addressed the effects of a prebiotic, xylooligosaccharide (XOS), on the gut microbiota and ear inflammation in an oxazolone-induced dermatitis model in BALB/c mice. Mice were fed a XOS supplemented or a control diet throughout the experiment. Ear thickness and clinical skin inflammation were scored blindly after three weeks topical challenge with 0.4% oxazolone. The mice were divided into high and low responders to oxazolone-induced dermatitis based on clinical inflammation and histological evaluation of ear biopsies, and significantly fewer high responders were present in the XOS fed group. In addition, XOS fed mice had higher abundance of Prevotella spp. in their gut microbiota compared to the control fed mice. Serum IgE and ear tissue cytokine levels correlated significantly with the clinical scores, and with the abundance of Prevotella spp. The strong association between the low-responding phenotype and high abundance of Prevotella spp., indicates an alleviating effect of this intestinal colonizer in allergic sensitization. Prevotella should be considered as a relevant target for future microbiota-directed treatment strategies in atopic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-78404-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713185PMC
December 2020

Color of Colon Content of Normal and Intrauterine Growth-Restricted Weaned Piglets is Associated with Specific Microbial Taxa and Physiological Parameters.

Animals (Basel) 2020 Jun 22;10(6). Epub 2020 Jun 22.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK- 1870 Frederiksberg C, Denmark.

A well-balanced gut microbiome is associated with improved health outcomes, but to date, the GM of IUGR piglets have only been sparsely investigated. Here, we investigated GM composition, color of colon content, and blood parameters of 20 IUGR and 20 normal 24-day-old piglets. No significant differences were detected in colon microbiota composition between IUGR and the normal piglets with respect to alpha and beta diversity measures. The colon content of these piglets displayed three colors: brown, black, and yellow. Interestingly, the color of the colon content varied with microbial community composition, with significant differences in the relative abundance of taxa belonging to Fusobacteria and Treponema. Fusobacteria were most abundant in yellow fecal samples, with a mean relative abundance around 5.6%, whereas this was 0.51% within brown and 0.02% for the black fecal samples. Fusobacteria positively correlated with total blood protein, albumin, and triglycerides. Contrarily, was at 0.9% the most abundant in black fecal samples, while present at 0.1% of relative abundance in brown fecal samples and 0.01% in yellow samples, correlating positively with blood iron content. This study indicates that colon/fecal content color can be used as indicator for specific GM and metabolite signatures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani10061073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341333PMC
June 2020

Metabolic Effects of Bovine Milk Oligosaccharides on Selected Commensals of the Infant Microbiome-Commensalism and Postbiotic Effects.

Metabolites 2020 Apr 24;10(4). Epub 2020 Apr 24.

Department of Food Science, Aarhus University, Agro Food Park 48, 8200 Aarhus N, Denmark.

Oligosaccharides from human or bovine milk selectively stimulate growth or metabolism of bacteria associated with the lower gastrointestinal tract of infants. Results from complex infant-type co-cultures point toward a possible synergistic effect of combining bovine milk oligosaccharides (BMO) and lactose (LAC) on enhancing the metabolism of subsp. and inhibition of We examine the interaction between subsp. and the commensal , by culturing them in mono- and co-culture with different carbohydrates available. To understand the interaction between BMO and lactose on . subsp. and test the potential postbiotic effect on growth and/or metabolic activity, we inoculated into fresh media and compared the metabolic changes to in cell-free supernatant from subsp. fermented media. In co-culture, subsp. benefits from (commensalism), especially in a lactose-rich environment. Furthermore, subsp. fermentation of BMO + LAC impaired ' ability to utilize BMO as a carbon source (potential postbiotic effect).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo10040167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240951PMC
April 2020

Fermentable Dietary Fiber Promotes Helminth Infection and Exacerbates Host Inflammatory Responses.

J Immunol 2020 06 13;204(11):3042-3055. Epub 2020 Apr 13.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C DK-1870, Denmark;

Fermentable dietary fibers promote the growth of beneficial bacteria, can enhance mucosal barrier integrity, and reduce chronic inflammation. However, effects on intestinal type 2 immune function remain unclear. In this study, we used the murine whipworm to investigate the effect of the fermentable fiber inulin on host responses to infection regimes that promote distinct Th1 and Th2 responses in C57BL/6 mice. In uninfected mice, dietary inulin stimulated the growth of beneficial bacteria, such as (Actinobacteria) and (Verrucomicrobia). Despite this, inulin prevented worm expulsion in normally resistant mice, instead resulting in chronic infection, whereas mice fed an equivalent amount of nonfermentable fiber (cellulose) expelled worms normally. Lack of expulsion in the mice fed inulin was accompanied by a significantly Th1-skewed immune profile characterized by increased T-bet T cells and IFN-γ production in mesenteric lymph nodes, increased expression of in the cecum, and a complete absence of mast cell and IgE production. Furthermore, the combination of dietary inulin and high-dose infection caused marked dysbiosis, with expansion of the Firmicutes and Proteobacteria phyla, near elimination of Bacteroidetes, and marked reductions in cecal short-chain fatty acids. Neutralization of IFN-γ during infection abrogated expression and was sufficient to restore IgE production and worm expulsion in inulin-fed mice. Our results indicate that, whereas inulin promoted gut health in otherwise healthy mice, during infection, it exacerbated inflammatory responses and dysbiosis. Thus, the positive effects of fermentable fiber on gut inflammation appear to be context dependent, revealing a novel interaction between diet and infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1901149DOI Listing
June 2020

Dietary Inulin and Infection Promote Beneficial Bacteria Throughout the Porcine Gut.

Front Microbiol 2020 4;11:312. Epub 2020 Mar 4.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.

The gut microbiota (GM) displays a profound ability to adapt to extrinsic factors, such as gastrointestinal pathogens and/or dietary alterations. Parasitic worms (helminths) and host-associated GM share a long co-evolutionary relationship, exerting mutually modulatory effects which may impact the health of the host. Moreover, dietary components such as prebiotic fibers (e.g. inulin) are capable of modulating microbiota toward a composition often associated with a healthier gut function. The effect of helminth infection on the host microbiota is still equivocal, and it is also unclear how parasites and prebiotic dietary components interact to influence the microbiota and host health status. Some helminths, such as (porcine whipworm), also exhibit strong immunomodulatory and anti-inflammatory effects. We therefore explored the effects of , alone and in interaction with inulin, both in fecal microbiota during the infection period and luminal microbiota across four intestinal segments at the end of a 4-week infection period. We observed that generally had minimal, but mainly positive, effects on the microbiota. increased the relative abundance of bacterial genera putatively associated with gut health such as , and decreased bacteria such as Proteobacteria that have been associated with dysbiosis. Interestingly, dietary inulin interacted with to enhance these effects, thereby modulating the microbiota toward a composition associated with reduced inflammation. Our results show that administration of together with the consumption of prebiotic inulin may have the potential to positively affect gut health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.00312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064446PMC
March 2020

Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia: The impact of the gut microbiota.

Int J Cancer 2020 10 16;147(7):1953-1962. Epub 2020 Mar 16.

Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Intestinal mucositis is a common side effect of chemotherapy leading to diarrhea, abdominal pain and increased risk of infections. The intestinal microbiota has been recognized as a key regulator of mucosal immune responses. Therefore, we hypothesized that intestinal microbial changes would be associated with enterocyte loss and systemic inflammation during induction treatment for childhood acute lymphoblastic leukemia (ALL). We prospectively included 51 children newly-diagnosed with ALL treated in Denmark in 2015-2018. Plasma C-reactive protein (CRP), plasma citrulline (marker of functional enterocytes mass) measurements and fecal samplings were performed on treatment Days 1, 8, 15, 22 and 29. Moreover, intestinal mucositis was scored by a trained nurse/physician. Fecal samples in patients and 19 healthy siblings were analyzed by 16S rRNA gene sequencing (V3-V4 region). Bacterial alpha diversity was lower in patients compared to siblings. It decreased from Day 1 to Days 8-22 and increased on Day 29. Shannon alpha diversity index was correlated with CRP on Days 15-29 (rho = -0.33-0.49; p < 0.05) and with citrulline on Days 15 and 29 (although with p values <0.06, rho = 0.32-0.34). The abundance of unclassified Enterococcus species (spp.) was correlated with CRP on Days 22-29 (rho = 0.42-0.49; p < 0.009), while the abundance of unclassified Lachnospiraceae spp. was correlated with citrulline on days 8-15 (rho = 0.48-0.62, p < 0.001). Systemic inflammation, enterocyte loss and relative abundance of unclassified Enterococcus spp. reached a peak around Day 15. In conclusion, specific changes in the microbiota were associated with the severity of enterocyte loss and systemic inflammation during chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32942DOI Listing
October 2020

Pretreatment Prevotella-to-Bacteroides ratio and salivary amylase gene copy number as prognostic markers for dietary weight loss.

Am J Clin Nutr 2020 05;111(5):1079-1086

Department of Nutrition, Exercise, and Sports, Faculty of Sciences, University of Copenhagen, Denmark.

Background: The inconsistent link observed between salivary amylase gene copy number (AMY1 CN) and weight management is likely modified by diet and microbiome.

Objective: Based on analysis of a previously published study, we investigated the hypothesis that interaction between diet, Prevotella-to-Bacteriodes ratio (P/B ratio), and AMY1 CN influence weight change.

Methods: Sixty-two people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber, whole grain, intrinsic sugars, and starch or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Before subjects were randomly assigned to receive the NND or ADD diet, blood and fecal samples were collected, from which AMY1 CN and P/B ratio, respectively, were determined. Body weight change was described by using linear mixed models, including biomarker [log10(P/B ratio) and/or AMY1 CN] diet-group interactions.

Results: Baseline means ± SDs of log10(P/B ratio) and AMY1 CN were -2.1 ± 1.8 and 6.6 ± 2.4, respectively. Baseline P/B ratio predicted a 0.99-kg/unit (95% CI: 0.40, 1.57; n = 54; P < 0.001) higher weight loss for those subjects on the NND compared with those on the ADD diet, whereas AMY1 CN was not found to predict weight loss differences between the NND and ADD groups [0.05 kg/CN (95% CI: -0.40, 0.51; n = 54; P = 0.83)]. However, among subjects with low AMY1 CN (<6.5 copies), baseline P/B ratio predicted a 2.12-kg/unit (95% CI: 1.37, 2.88; n = 30; P < 0.001) higher weight loss for the NND group than the ADD group. No such differences in weight loss were found among subjects in both groups with high AMY1 CN [-0.17 kg/unit (95% CI: -1.01, 0.66; n = 24; P = 0.68)].

Conclusions: The combined use of low AMY1 CN and pretreatment P/B ratio for weight loss prediction led to highly individualized weight loss results with the introduction of more fiber, whole grain, intrinsic sugars, and starch in the diet. These preliminary observations suggest that more undigested starch reaches the colon in individuals with low AMY1 CN, and that the fate of this starch depends on the gut microbiota composition. This trial was registered at clinicaltrials.gov as NCT01195610.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqaa007DOI Listing
May 2020

Physical fitness in community-dwelling older adults is linked to dietary intake, gut microbiota, and metabolomic signatures.

Aging Cell 2020 03 22;19(3):e13105. Epub 2020 Jan 22.

Department of Food Science, University of Copenhagen, Frederiksberg C, Denmark.

When humans age, changes in body composition arise along with lifestyle-associated disorders influencing fitness and physical decline. Here we provide a comprehensive view of dietary intake, physical activity, gut microbiota (GM), and host metabolome in relation to physical fitness of 207 community-dwelling subjects aged +65 years. Stratification on anthropometric/body composition/physical performance measurements (ABPm) variables identified two phenotypes (high/low-fitness) clearly linked to dietary intake, physical activity, GM, and host metabolome patterns. Strikingly, despite a higher energy intake high-fitness subjects were characterized by leaner bodies and lower fasting proinsulin-C-peptide/blood glucose levels in a mechanism likely driven by higher dietary fiber intake, physical activity and increased abundance of Bifidobacteriales and Clostridiales species in GM and associated metabolites (i.e., enterolactone). These factors explained 50.1% of the individual variation in physical fitness. We propose that targeting dietary strategies for modulation of GM and host metabolome interactions may allow establishing therapeutic approaches to delay and possibly revert comorbidities of aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acel.13105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059135PMC
March 2020

Restitution of gut microbiota in Ugandan children administered with probiotics ( GG and subsp. BB-12) during treatment for severe acute malnutrition.

Gut Microbes 2020 07 20;11(4):855-867. Epub 2020 Jan 20.

Department of Food Science, University of Copenhagen , Frederiksberg C, Denmark.

Severe acute malnutrition (SAM) is a major challenge in low-income countries and gut microbiota (GM) dysbiosis may play a role in its etiology. Here, we determined the GM evolution during rehabilitation from SAM and the impact of probiotics ( GG and subsp. lactis BB-12) supplementation. The GM (16S rRNA gene amplicon sequencing) of children admitted to hospital with SAM showed distinct composition over admission (e.g. spp., and Enterobacteriaceae spp.), discharge (e.g. Clostridiaceae spp., ) and follow-up (e.g. spp., ), reaching similar β- and α-diversity as healthy individuals. Children with diarrhea had reduced distribution of Bacteroidaceae, Lachnospiraceae, increased Enterobacteriaceae and Moraxellaceae, and lower α-diversity. Children suffering from edematous SAM had diminished proportion of Prevotellaceae, Lachnospiraceae, Ruminoccaceae and a higher α-diversity when compared to non-edematous SAM. Supplementation of probiotics did not influence β-diversity upon discharge or follow-up, but it increased ( < .05) the number of observed species [SE: > 4.5]. Children where the probiotic species were detected had lower cumulative incidence ( < .001) of diarrhea during the follow-up period compared to children receiving placebo and children receiving probiotics, but where the probiotics were not detected. The GM of children with non-edematous and edematous SAM differ in composition, which might have implications for future GM targeted treatments. Probiotics treatment reduced the cumulative incidence of diarrhea during the outpatient phase, with the strongest effect in children where the administered probiotics could be detected in the GM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/19490976.2020.1712982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524335PMC
July 2020

Virulent coliphages in 1-year-old children fecal samples are fewer, but more infectious than temperate coliphages.

Nat Commun 2020 01 17;11(1):378. Epub 2020 Jan 17.

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France.

Bacteriophages constitute an important part of the human gut microbiota, but their impact on this community is largely unknown. Here, we cultivate temperate phages produced by 900 E. coli strains isolated from 648 fecal samples from 1-year-old children and obtain coliphages directly from the viral fraction of the same fecal samples. We find that 63% of strains hosted phages, while 24% of the viromes contain 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-14042-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969025PMC
January 2020

Impact of Dietary Supplementation of Fermented Rapeseed with or without Macroalgae on Performance and Health of Piglets Following Omission of Medicinal Zinc from Weaner Diets.

Animals (Basel) 2020 Jan 15;10(1). Epub 2020 Jan 15.

Department of Animal Sciences, Faculty of Technical Sciences, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark.

The feeding of medicinal zinc oxide (ZnO) to weaner piglets will be phased out after 2022 in Europe, leaving pig producers without options to manage post-weaning disorders. This study assessed whether rapeseed meal, fermented alone (FRM) or co-fermented with a single (; FRMA), or two ( and ; FRMAS) brown macroalagae species, could improve weaner piglet performance and stimulate intestinal development as well as maturation of gut microbiota in the absence of in-feed zinc. Weaned piglets (n = 1240) were fed, during 28-85 days of age, a basal diet with no additives (negative control; NC), 2500 ppm in-feed ZnO (positive control; PC), FRM, FRMA or FRMAS. Piglets fed FRM and FRMA had a similar or numerically improved, respectively, production performance compared to PC piglets. Jejunal villus development was stimulated over NC in PC, FRM and FRMAS (gender-specific). FRM enhanced colon mucosal development and reduced signs of intestinal inflammation. All fermented feeds and PC induced similar changes in the composition and diversity of colon microbiota compared to NC. In conclusion, piglet performance, intestinal development and health indicators were sustained or numerically improved when in-feed zinc was replaced by FRM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani10010137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023219PMC
January 2020

Microbiota in foods from Inuit traditional hunting.

PLoS One 2020 14;15(1):e0227819. Epub 2020 Jan 14.

Department of Food Science, The University of Copenhagen, Frederiksberg, Denmark.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227819PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959823PMC
April 2020

Severe gut microbiota dysbiosis caused by malnourishment can be partly restored during 3 weeks of refeeding with fortified corn-soy-blend in a piglet model of childhood malnutrition.

BMC Microbiol 2019 12 10;19(1):277. Epub 2019 Dec 10.

Department of Food Science, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg C, Denmark.

Background: Childhood malnutrition is a global health challenge associated with multiple adverse consequences, including delayed maturation of the gut microbiota (GM) which might induce long-term immune dysfunction and stunting. To understand GM dynamics during malnutrition and subsequent re-feeding, we used a piglet model with a malnutrition-induced phenotype similar to humans. Piglets were weaned at the age of 4 weeks, fed a nutritionally optimal diet for 1 week post-weaning before being fed a pure maize diet for 7 weeks to induce symptoms of malnutrition. After malnourishment, the piglets were re-fed using different regimes all based on general food aid products, namely Corn-Soy blend (CSB) fortified with phosphorus (CSB+), CSB fortified with phosphorus and skim milk powder (CSB++) and CSB fortified with phosphorus and added whey permeate (CSB + P).

Results: Malnourishment had profound impact on the GM of the piglets leading to a less diverse GM dominated especially by Akkermansia spp. as determined by 16S rRNA gene amplicon sequencing. All three re-feeding regimes partly restored GM, leading to a more diverse GM compositionally closer to that of well-nourished piglets. This effect was even more pronounced for CSB++ compared to CSB+ and CSB + P.

Conclusion: The GM of piglets were profoundly disturbed by malnourishment resulting in significantly increased abundance of Akkermansia spp. CSB++ may have superior effect on recovering GM diversity compared to the two other food aid products used in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-019-1658-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902335PMC
December 2019

DNA enrichment and tagmentation method for species-level identification and strain-level differentiation using ON-rep-seq.

Commun Biol 2019 10;2:369. Epub 2019 Oct 10.

1Food Microbiology and Fermentation, Department of Food Science, University of Copenhagen, 1958 Frederiksberg C, Denmark.

Despite the massive developments within culture-independent methods for detection of microorganisms during the last decade, culture-based methods remain a cornerstone in microbiology. Yet, the problem of rapid, accurate and inexpensive identification of bacterial isolates down to species/strain level remains unresolved. We have developed a new method for bacterial DNA enrichment and tagmentation allowing fast (<24 h) and cost-effective species level identification and strain level differentiation using the MinION portable sequencing platform (ON-rep-seq). DNA library preparation for 96 isolates takes less than 5 h and ensures highly reproducible distribution of reads that can be used to generate strain level specific read length counts profiles (LCp). We have developed a pipeline that by correcting reads error within peaks of LCp generates a set of high quality (>99%) consensus reads. Whereas, the information from high quality reads is used to retrieve species level taxonomy, comparison of LCp allows for strain level differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-019-0617-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787052PMC
May 2020

Short communication: Gut microbial colonization of the mouse colon using faecal transfer was equally effective when comparing rectal inoculation and oral inoculation based on 16S rRNA sequencing.

Res Vet Sci 2019 Oct 17;126:227-232. Epub 2019 Sep 17.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1871 Frederiksberg C, Denmark.

In the present study we hypothesized that a higher degree of gut microbiota (GM) transfer and colonization could be reached by rectal inoculation compared to oral inoculation, which is commonly used in mouse studies for GM transfer. We treated C57BL/6NTac Specific Pathogen Free (SPF) mice with antibiotics and subsequently we inoculated these with GM from donor mice of the same strain by either the oral or the rectal inoculation method. 16S rRNA gene sequencing of the colon microbiota showed no difference in microbial community on account of inoculation method as determined by unweighted UniFrac distance metrics in C57BL/6NTac SPF mice. In addition, qPCR analysis on colon tissue revealed no difference in mRNA expression between the inoculation methods. Next, the SPF mice were compared to germ-free (GF)-mice to identify differences in inoculation efficacy. Whether the mice were antibiotic treated SPF or GF clearly influenced GM determined by 16S rRNA gene sequencing where the SPF mice experienced up-regulation of S24-7 (p = .0001) and a decrease in Rikenellaceae (p = .016) compared to GF mice. qPCR analysis on colon tissue revealed up-regulation in mRNA gene expression of Il6, Il10, Reg3g and transcription factor RORγt (Rorc) in GF mice compared to SPF mice on a significant level (p < .05). This gene expression profile is consistent with post colonization development of the intestinal barrier in GF mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rvsc.2019.09.009DOI Listing
October 2019

Prevotella Abundance Predicts Weight Loss Success in Healthy, Overweight Adults Consuming a Whole-Grain Diet Ad Libitum: A Post Hoc Analysis of a 6-Wk Randomized Controlled Trial.

J Nutr 2019 12;149(12):2174-2181

Department of Nutrition, Exercise, and Sports, University of Copenhagen, Denmark.

Background: The key to effective weight loss may be to match diet and gut microbes, since recent studies have found that subjects with high Prevotella abundances in their gut microbiota lose more weight on diets rich in fiber than subjects with low Prevotella abundances.

Objectives: We reanalyzed a 6-wk, parallel, randomized trial to investigate difference in body weight changes when participants, stratified by fecal microbiota composition, consumed ad libitum a whole-grain (WG) or a refined-wheat (RW) diet.

Methods: We stratified 46 (19 men, 27 women; ages 30-65 y) healthy, overweight adults by baseline Prevotella-to-Bacteroides ratios and Prevotella abundances. Subjects with no Prevotella were analyzed separately (n = 24). Compared with the RW diet (mean = 221 g/d), the WG diet (mean = 228 g/d) had a higher fiber content (33 g/d compared with 23 g/d). Linear mixed models and correlations were applied to link 6-wk changes in body weights and metabolic and microbiota markers, according to Prevotella groups and diets.

Results: The Prevotella abundances correlated inversely with weight changes (r = -0.34; P = 0.043). Consequently, subjects with high Prevotella abundances (n = 15) spontaneously lost 1.80 kg (95% CI: -3.23, -0.37 kg; P = 0.013) more on the WG diet than on the RW diet, whereas those with low Prevotella abundances (n = 31) were weight stable (-0.22 kg; 95% CI: -1.40, 0.96 kg; P = 0.72). Thus, the mean difference between the Prevotella groups was 2.02 kg (95% CI: -3.87, -0.17 kg; P = 0.032). Subjects with no Prevotella lost 1.59 kg (95% CI: -2.65, -0.52 kg; P = 0.004) more on the WG diet than on the RW diet. No 6-wk changes in appetite sensations, glucose metabolisms, or fecal SCFAs were associated with the Prevotella groups.

Conclusions: Healthy, overweight adults with high Prevotella abundances lost more weight than subjects with low Prevotella abundances when consuming a diet rich in WG and fiber ad libitum for 6 wk. This further supports enterotypes as a potential biomarker in personalized nutrition for obesity management. This t rial was registered at clinicaltrials.gov as NCT02358122.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jn/nxz198DOI Listing
December 2019
-->