Seed Location Impacts Whole-Brain Structural Network Comparisons between Healthy Elderly and Individuals with Alzheimer’s Disease

Whole-brain networks derived from diffusion tensor imaging (DTI) data require the identification of seed and target regions of interest (ROIs) to assess connectivity patterns. This study investigated how initiating tracts from gray matter (GM) or white matter (WM) seed ROIs impacts (1) structural networks constructed from DTI data from healthy elderly (control) and individuals with Alzheimer’s disease (AD) and (2) between-group comparisons using these networks. DTI datasets were obtained from the Alzheimer’s disease Neuroimaging Initiative database. Deterministic tractography was used to build two whole-brain networks for each subject; one in which tracts were initiated from WM ROIs and another in which they were initiated from GM ROIs. With respect to the first goal, in both groups, WM-seeded networks had approximately 400 more connections and stronger connections (as measured by number of streamlines per connection) than GM-seeded networks, but shared 94% of the connections found in the GM-seed networks. With respect to the second goal, between-group comparisons revealed a stronger subnetwork (as measured by number of streamlines per connection) in controls compared to AD using both WM-seeded and GM-seeded networks. The comparison using WM-seeded networks produced a larger (i.e., a greater number of connections) and more significant subnetwork in controls versus AD. Global, local, and nodal efficiency were greater in controls compared to AD, and between-group comparisons of these measures using WM-seeded networks had larger effect sizes than those using GM-seeded networks. These findings affirm that seed location significantly affects the ability to detect between-group differences in structural networks

Antibiotic prophylaxis and hospitalization of horses subjected to median laparotomy: gut microbiota trajectories and abundance increase of Escherichia

Introduction: Horse clinics are hotspots for the accumulation and spread of clinically relevant and zoonotic multidrug-resistant bacteria, including extended-spectrum β-lactamase producing (ESBL) Enterobacterales. Although median laparotomy in cases of acute equine colic is a frequently performed surgical intervention, knowledge about the effects of peri-operative antibiotic prophylaxis (PAP) based on a combination of penicillin and gentamicin on the gut microbiota is limited. Methods: We collected fecal samples of horses from a non-hospitalized control group (CG) and from horses receiving either a pre-surgical single-shot (SSG) or a peri-operative 5-day (5DG) course of PAP. To assess differences between the two PAP regimens and the CG, all samples obtained at hospital admission (t0), on days three (t1) and 10 (t2) after surgery, were screened for ESBL-producing Enterobacterales and subjected to 16S rRNA V1–V2 gene sequencing. Results: We included 48 samples in the SSG (n = 16 horses), 45 in the 5DG (n = 15), and 20 in the CG (for t0 and t1, n = 10). Two samples of equine patients receiving antibiotic prophylaxis (6.5%) were positive for ESBL-producing Enterobacterales at t0, while this rate increased to 67% at t1 and decreased only slightly at t2 (61%). Shannon diversity index (SDI) was used to evaluate alpha-diversity changes, revealing there was no significant difference between horses suffering from acute colic (5DG, SDImean of 5.90, SSG, SDImean of 6.17) when compared to the CG (SDImean of 6.53) at t0. Alpha-diversity decreased significantly in both PAP groups at t1, while at t2 the onset of microbiome recovery was noticed. Although we did not identify a significant SDImean difference with respect to PAP duration, the community structure (beta-diversity) was considerably restricted in samples of the 5DG at t1, most likely due to the ongoing administration of antibiotics. An increased abundance of Enterobacteriaceae, especially Escherichia, was noted for both study groups at t1. Conclusion: Colic surgery and PAP drive the equine gut microbiome towards dysbiosis and reduced biodiversity that is accompanied by an increase of samples positive for ESBL-producing Enterobacterales. Further studies are needed to reveal important factors promoting the increase and residency of ESBL-producing Enterobacterales among hospitalized horses

The role of the gut microbiome in the association between habitual anthocyanin intake and visceral abdominal fat in population-level analysis

BACKGROUND: Flavonoid intake modifies the composition of the gut microbiome, which contributes to the metabolism of flavonoids. Few studies have examined the contribution of the gut microbiome to the health benefits associated with flavonoid intake. OBJECTIVES: We aimed to examine associations between habitual intakes of flavonoid subclasses and MRI-determined visceral (VAT) and subcutaneous (SAT) adipose tissue. Uniquely, we also identified associations between the aforementioned measurements and gut microbiome composition sequenced from 16S ribosomal RNA genes. METHODS: We undertook cross-sectional analyses of 618 men and women (n = 368 male), aged 25-83 y, from the PopGen cohort. RESULTS: Higher intake of anthocyanins was associated with lower amounts of VAT [tertile (T)3-T1: -0.49 dm3; β: -8.9%; 95% CI: -16.2%, -1.1%; P = 0.03] and VAT:SAT ratio (T3-T1: -0.04; β: -7.1%; 95% CI: -13.5%, -0.3%; P = 0.03). Higher intakes of anthocyanin-rich foods were also inversely associated with VAT [quantile (Q)4-Q1: -0.39 dm3; β: -9.9%; 95% CI: -17.4%, -1.6%; P = 0.02] and VAT:SAT ratio (Q4-Q1: -0.04; β: -6.5%; 95% CI: -13.3%, -0.9%; P = 0.03). Participants with the highest intakes of anthocyanin-rich foods also had higher microbial diversity (Q4-Q1: β: 0.18; 95% CI: 0.06, 0.31; P < 0.01), higher abundances of Clostridiales (Q4-Q1: β: 449; 95% CI: 96.3, 801; P = 0.04) and Ruminococcaceae (Q4-Q1: β: 313; 95% CI: 33.6, 591; P = 0.04), and lower abundance of Clostridium XIVa (Q4-Q1: β: -41.1; 95% CI: -72.4, -9.8; P = 0.04). Participants with the highest microbial diversity, abundances of Clostridiales and Ruminococcaceae, and lower abundance of Clostridium XIVa had lower amounts of VAT. Up to 18.5% of the association between intake of anthocyanin-rich foods and VAT could be explained by the gut microbiome. CONCLUSIONS: These novel data suggest that higher microbial diversity and abundance of specific taxa in the Clostridiales order may contribute to the association between higher intake of anthocyanins and lower abdominal adipose tissue

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by recessive mutations in the AIRE gene. The hallmark of the disease is the production of highly neutralizing autoantibodies against type I interferons and IL-22. Considering the importance of IL-22 in maintaining mucosal barrier integrity and shaping its microbial community, we sought to study potential changes in the oral cavity in this model of human IL-22 paucity. We found that besides known Th22 cell deficiency, APECED patients have significantly fewer circulating MAIT cells with potential IL-22 secreting capacity. Saliva samples from APECED patients revealed local inflammation, the presence of autoantibodies against IFN-α and IL-22, and alterations in the oral microbiota. Moreover, gene expression data of buccal biopsy samples suggested impaired antimicrobial response and cell proliferation, both of which are processes regulated by IL-22. Our data complement the knowledge gained from mouse models and support the concept of IL-22 being a critical homeostatic cytokine in human mucosal sites

Ecology impacts the decrease of Spirochaetes and Prevotella in the fecal gut microbiota of urban humans

Compared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets - especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis. In total, 368 stool samples from 38 different animal species, including Homo sapiens, belonging to four diverse mammalian orders were collected at seven different locations and analyzed by 16S rRNA gene amplicon sequencing. Comprehensive data analysis was performed to (i) determine the overall impact of host phylogeny vs. diet, location, and ecology and to (ii) examine the general pattern of fecal bacterial diversity across captive mammals and humans.By using a controlled study design with captive mammals we could verify that host phylogeny is the most dominant driver of mammalian gut microbiota composition. However, the effect of ecology appears to be able to overcome host phylogeny and should therefore be studied in more detail in future studies. Most importantly, our study could observe a remarkable decrease of Spirochaetes and Prevotella in westernized humans and platyrrhines, which is probably not only due to diet, but also to the social behavior and structure in these communities.Our study highlights the importance of phylogenetic relationship and ecology within the evolution of mammalian fecal microbiota composition. Particularly, the observed decrease of Spirochaetes and Prevotella in westernized communities might be associated to lifestyle dependent rapid evolutionary changes, potentially involved in the establishment of dysbiotic microbiomes, which promote the etiology of chronic diseases

Helicobacter pylori infection associates with fecal microbiota composition and diversity

Helicobacter (H.) pylori is the most important cause for peptic ulcer disease and a risk factor for gastric carcinoma. How colonization with H. pylori affects the intestinal microbiota composition in humans is unknown. We investigated the association of H. pylori infection with intestinal microbiota composition in the population-based cohort Study-of-Health-in-Pomerania (SHIP)-TREND. Anti-H. pylori serology and H. pylori stool antigen tests were used to determine the H. pylori infection status. The fecal microbiota composition of 212 H. pylori positive subjects and 212 matched negative control individuals was assessed using 16S rRNA gene sequencing. H. pylori infection was found to be significantly associated with fecal microbiota alterations and a general increase in fecal microbial diversity. In infected individuals, the H. pylori stool antigen load determined a larger portion of the microbial variation than age or sex. The highest H. pylori stool antigen loads were associated with a putatively harmful microbiota composition. This study demonstrates profound alterations in human fecal microbiota of H. pylori infected individuals. While the increased microbiota diversity associated with H. pylori infection as well as changes in abundance of specific genera could be considered to be beneficial, others may be associated with adverse health effects, reflecting the complex relationship between H. pylori and its human host

Host traits, lifestyle and environment are associated with the human skin bacteria

BackgroundThe human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts to the broader knowledge about the factors influencing the gut microbiota.ObjectivesWe aimed to investigate major patterns of associations of host traits, lifestyle, and environmental factors with skin bacteria in two German populations.MethodsThis is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n=294) and KORA FF4 (n=353), totaling 1794 skin samples. The V1-V2 regions of the 16S rRNA gene were sequenced. Associations were tested with two bacterial levels, community (beta-diversity) and 16S rRNA gene amplicon sequence variants (ASVs).ResultsWe validated known associations of the skin microbiota with skin microenvironment, age, body mass index (BMI) and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education, and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium, and Staphylococcus.DiscussionWe expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with the skin bacteria. Finally, we hypothesize that the skin microenvironment and the host physiology would shape the skin bacterial community at greater extent in comparison to a single skin physiological feature, lifestyle and environmental exposition

Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study

Background Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements. Conclusions We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology. Trial registration DRKS, DRKS00015873 . Registered 12 December 2018; Retrospectively registered

Antibiotic prophylaxis and hospitalization of horses subjected to median laparotomy: gut microbiota trajectories and abundance increase of Escherichia

IntroductionHorse clinics are hotspots for the accumulation and spread of clinically relevant and zoonotic multidrug-resistant bacteria, including extended-spectrum β-lactamase producing (ESBL) Enterobacterales. Although median laparotomy in cases of acute equine colic is a frequently performed surgical intervention, knowledge about the effects of peri-operative antibiotic prophylaxis (PAP) based on a combination of penicillin and gentamicin on the gut microbiota is limited.MethodsWe collected fecal samples of horses from a non-hospitalized control group (CG) and from horses receiving either a pre-surgical single-shot (SSG) or a peri-operative 5-day (5DG) course of PAP. To assess differences between the two PAP regimens and the CG, all samples obtained at hospital admission (t0), on days three (t1) and 10 (t2) after surgery, were screened for ESBL-producing Enterobacterales and subjected to 16S rRNA V1–V2 gene sequencing.ResultsWe included 48 samples in the SSG (n = 16 horses), 45 in the 5DG (n = 15), and 20 in the CG (for t0 and t1, n = 10). Two samples of equine patients receiving antibiotic prophylaxis (6.5%) were positive for ESBL-producing Enterobacterales at t0, while this rate increased to 67% at t1 and decreased only slightly at t2 (61%). Shannon diversity index (SDI) was used to evaluate alpha-diversity changes, revealing there was no significant difference between horses suffering from acute colic (5DG, SDImean of 5.90, SSG, SDImean of 6.17) when compared to the CG (SDImean of 6.53) at t0. Alpha-diversity decreased significantly in both PAP groups at t1, while at t2 the onset of microbiome recovery was noticed. Although we did not identify a significant SDImean difference with respect to PAP duration, the community structure (beta-diversity) was considerably restricted in samples of the 5DG at t1, most likely due to the ongoing administration of antibiotics. An increased abundance of Enterobacteriaceae, especially Escherichia, was noted for both study groups at t1.ConclusionColic surgery and PAP drive the equine gut microbiome towards dysbiosis and reduced biodiversity that is accompanied by an increase of samples positive for ESBL-producing Enterobacterales. Further studies are needed to reveal important factors promoting the increase and residency of ESBL-producing Enterobacterales among hospitalized horses