scholarly journals Dynamic Changes of Gut Microbiome and Immune Response During the Acute Stage of Stroke in a Pig Model (P14-012-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Julie Jeon ◽  
Jeferson Lourenco ◽  
Erin Kaiser ◽  
Elizabeth Waters ◽  
Kelly Scheulin ◽  
...  

Abstract Objectives Stroke is a leading cause of mortality and disability in the United States. Secondary injuries induced by inflammation plays a critical role in stroke recovery. This study investigates gut microbiome changes during the acute stage of ischemic stroke to better understand the role of gut microbiome in inflammation in an ischemic stroke pig model. Methods Ischemic stroke was induced by middle cerebral artery occlusion in pigs (n = 7). Fecal samples were collected at pre-stoke (PRE), 1 (1DPS), 3 (3DPS), and 5 days post-stroke (5DPS) to measure gut microbiome composition. Blood samples were collected at 1DPS for white blood cell analysis. Results Ischemic stroke was confirmed by magnetic resonance imaging at 1DPS. The dominant pre-stroke fecal bacterial phyla (>1% relative abundance) were Firmicutes (89.2%), Bacteroidetes (3.7%), Actinobacteria (2.0%) and Proteobacteria (1.3%). This composition significantly (P < 0.05) differed at 3DPS with a decreased Firmicutes (68.1%) and increased Actinobacteria (3.70%) and Proteobacteria (19.0%), and a trending (P = 0.06) increase among Bacteroidetes (7.6%). At 5DPS, Bacteroidetes (7.6%) remained elevated, but Firmicutes (86.6%), Actinobacteria (2.0%) and Proteobacteria (0.7%) returned to levels similar to PRE. At 1DPS, the α-diversity measured by Shannon index and species evenness were both decreased (P < 0.05), suggesting that overall bacterial diversity decreased immediately after the stroke. β-diversity analysis showed a trend for overall differences over time (P = 0.07), but no differences between specific days were found. Elevated inflammation and neutrophil-to-lymphocyte ratio (NLR) following stroke event have been related to negative functional outcome in stroke patients. At 1DPS, a significant increase in NLR was observed in the stroke pigs compared to those at PRE (P < 0.05), suggesting initiation of inflammatory response following stroke. Conclusions Ischemic stroke altered the gut microbiome composition, reduced microbiome diversity and increased immune response in pigs. Future studies are warranted to investigate systemic and neural inflammation mediated by the alteration of the gut microbiome following ischemic stroke. Funding Sources The study was funded by the National Institute of Health and University of Georgia (Faculty Research Grant).

2020 ◽  
Vol 14 ◽  
Author(s):  
Julie Jeon ◽  
Jeferson Lourenco ◽  
Erin E. Kaiser ◽  
Elizabeth S. Waters ◽  
Kelly M. Scheulin ◽  
...  

Stroke is a major cause of death and long-term disability affecting seven million adults in the United States each year. Recently, it has been demonstrated that neurological diseases, associated pathology, and susceptibility changes correlated with changes in the gut microbiota. However, changes in the microbial community in stroke has not been well characterized. The acute stage of stroke is a critical period for assessing injury severity, therapeutic intervention, and clinical prognosis. We investigated the changes in the gut microbiota composition and diversity using a middle cerebral artery (MCA) occlusion ischemic stroke pig model. Ischemic stroke was induced by cauterization of the MCA in pigs. Blood samples were collected prestroke and 4 h, 12 h, 1 day, and 5 days poststroke to evaluate circulating proinflammatory cytokines. Fecal samples were collected prestroke and 1, 3, and 5 days poststroke to assess gut microbiome changes. Results showed elevated systemic inflammation with increased plasma levels of tumor necrosis factor alpha at 4 h and interleukin-6 at 12 h poststroke, relative to prestroke. Microbial diversity and evenness were reduced at 1 day poststroke compared to prestroke. Microbial diversity at 3 days poststroke was negatively correlated with lesion volume. Moreover, beta-diversity analysis revealed trending overall differences over time, with the most significant changes in microbial patterns observed between prestroke and 3 days poststroke. Abundance of the Proteobacteria was significantly increased, while Firmicutes decreased at 3 days poststroke, compared to prestroke populations. Abundance of the lactic acid bacteria Lactobacillus was reduced at 3 days poststroke. By day 5, the microbial pattern returned to similar values as prestroke, suggesting the plasticity of gut microbiome in an acute period of stroke in a pig model. These findings provide a basis for characterizing gut microbial changes during the acute stage of stroke, which can be used to assess stroke pathology and the potential development of therapeutic targets.


2021 ◽  
Author(s):  
Joann Phan ◽  
Divya Nair ◽  
Suneer Jain ◽  
Thibaut Montagne ◽  
Demi Valeria Flores ◽  
...  

AbstractBackgroundIrritable bowel syndrome (IBS) is characterized by abdominal discomfort and irregular bowel movements and stool consistency. Because there are different symptoms associated with IBS, it is difficult to diagnose the role of the microbiome in IBS.ObjectiveHere, we present a study that includes metagenomic sequencing of stool samples from subjects with the predominant subtypes of IBS and a healthy cohort. We collected longitudinal samples from individuals with IBS who took daily made-to-order precision probiotic and prebiotic supplementation throughout the study.Materials and MethodsThis study includes a population of 489 individuals with IBS and 122 healthy controls. All stool samples were subjected to shotgun metagenomic sequencing. Precision probiotics and prebiotics were formulated for all subjects with longitudinal timepoints.ResultsThere was significant variation explained in the microbiome between the healthy and IBS cohorts. Individuals with IBS had a lower gut microbiome diversity and reduced anti-inflammatory microbes compared to the healthy controls. Eubacterium rectale and Faecalibacterium prausnitzii were associated with healthy microbiomes while Shigella species were associated with IBS. Pathway analysis indicated a functional imbalance of short chain fatty acids, vitamins, and a microbial component of Gram-negative bacteria in IBS compared to healthy controls. In the longitudinal dataset, there was a significant difference in microbiome composition between timepoints 1 and 3. There was also a significant increase in the overall microbiome score and relative abundances of probiotic species used to target the symptoms associated with IBS.ConclusionsWe identified microbes and pathways that differentiate healthy and IBS microbiomes. In response to precision probiotic supplementation, we identified a significant improvement in the overall microbiome score in individuals with IBS. These results suggest an important role for probiotics in managing IBS symptoms and modulation of the microbiome as a potential management strategy.ImportanceAn estimated 35 million people in the United States and 11.5% of the population globally are affected by IBS. Immunity, genetics, environment, diet, small intestinal bacterial overgrowth (SIBO), and the gut microbiome are all factors that contribute to the onset or triggers of IBS. With strong supporting evidence that the gut microbiome may influence symptoms associated with IBS, elucidating the important microbes that contribute to the symptoms and severity is important to make decisions for targeted treatment. As probiotics have become more common in treating IBS symptoms, identifying effective probiotics may help inform future studies and treatment.


Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 381 ◽  
Author(s):  
Magdalena Ruiz-Rodríguez ◽  
Manuel Martín-Vivaldi ◽  
Manuel Martínez-Bueno ◽  
Juan José Soler

Diet and host genetic or evolutionary history are considered the two main factors determining gut microbiota of animals, although studies are scarce in natural populations. The system of great spotted cuckoos (Clamator glandarius) parasitizing magpies (Pica pica) is ideal to study both effects since magpie adults feed cuckoo and magpie nestlings with the same diet and, consequently, differences in gut microbiota of nestlings of these two species will mainly reflect the importance of genetic components. Moreover, the diet of adults and of nestling cuckoos drastically differ from each other and, thus, differences and similarities in their microbiotas would respectively reflect the effect of environmental and genetic factors. We used next-generation sequencing technologies to analyze the gut microbiota of cuckoo adults and nestlings and of magpie nestlings. The highest α-diversity estimates appeared in nestling cuckoos and the lowest in nestling magpies. Moreover, despite the greatest differences in the microbiome composition of magpies and cuckoos of both ages, cuckoo nestlings harbored a mixture of the Operational Taxonomic Units (OTUs) present in adult cuckoos and nestling magpies. We identified the bacterial taxa responsible for such results. These results suggest important phylogenetic components determining gut microbiome of nestlings, and that diet might be responsible for similarities between gut microbiome of cuckoo and magpie nestlings that allow cuckoos to digest food provided by magpie adults.


2019 ◽  
Author(s):  
Petar Scepanovic ◽  
Flavia Hodel ◽  
Stanislas Mondot ◽  
Valentin Partula ◽  
Allyson Byrd ◽  
...  

ABSTRACTBackgroundThe gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1,000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20 – 69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.ResultsAmong 110 demographic, clinical and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between >5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics.ConclusionIn a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals.


Author(s):  
Johanna Reinold ◽  
Farnoush Farahpour ◽  
Christian Fehring ◽  
Sebastian Dolff ◽  
Margarethe Konik ◽  
...  

The gut microbiota contributes to maintaining human health and regulating immune responses. Severe COVID-19 illness is associated with a dysregulated pro-inflammatory immune response. The effect of SARS-CoV-2 on altering the gut microbiome and the relevance of the gut microbiome on COVID-19 severity needs to be clarified. In this prospective study, we analyzed the gut microbiome of 212 patients of a tertiary care hospital (117 patients infected with SARS-CoV-2 and 95 SARS-CoV-2 negative patients) using 16S rRNA gene sequencing of the V3-V4 region. Inflammatory markers and immune cells were quantified from blood. The gut microbiome in SARS-CoV-2 infected patients was characterized by a lower bacterial richness and distinct differences in the gut microbiome composition, including an enrichment of the phyla Proteobacteria and Bacteroidetes and a decrease of Actinobacteria compared to SARS-CoV-2 negative patients. The relative abundance of several genera including Bifidobacterium, Streptococcus and Collinsella was lower in SARS-CoV-2 positive patients while the abundance of Bacteroides and Enterobacteriaceae was increased. Higher pro-inflammatory blood markers and a lower CD8+ T cell number characterized patients with severe COVID-19 illness. The gut microbiome of patients with severe/critical COVID-19 exhibited a lower abundance of butyrate-producing genera Faecalibacterium and Roseburia and a reduction in the connectivity of a distinct network of anti-inflammatory genera that was observed in patients with mild COVID-19 illness and in SARS-CoV-2 negative patients. Dysbiosis of the gut microbiome associated with a pro-inflammatory signature may contribute to the hyperinflammatory immune response characterizing severe COVID-19 illness.


Author(s):  
Zoe J. Zreloff ◽  
Danielle Lange ◽  
Suzanne D. Vernon ◽  
Martha R. Carlin ◽  
Raul de Jesus Cano

Background. Inferior quality of biological material compromises data, slows discovery, and wastes research funds. The gut microbiome plays a critical role in human health and disease, yet little attention has been given to optimizing collection and processing methods of human stool. Methods. We collected the entire bowel movement from 2 healthy volunteers: one to examine stool sample heterogeneity and one to test stool sample handling parameters. Sequencing and bi-oinformatic analyses were used to examine the microbiome composition. Results. The microbiome profile varied depending on where the subsample was obtained from the stool. The exterior cortex of the stool was rich in specific phyla and deficient in others while the interior core of the stool revealed opposite microbiome profiles. Sample processing also re-sulted in varying microbiome profiles. Homogenization and stabilization at 4&deg;C gave superior microbial diversity profiles compared to the fresh or frozen subsamples of the same stool sample. Bacterial proliferation continued in the fresh subsample when processed at ambient temperature. Bacteroidetes proliferated and Firmicutes diminished during the 30-minute processing of fresh sample. The frozen sample had good overall diversity but Proteobacteria diminished likely be-cause of the freeze/thaw. Conclusions. The microbiome profile is specific to the section of the stool being sampled. Stool sample collection, homogenization, and stabilization at 4&deg;C for 24 hours provides a &ldquo;neat&rdquo;, high-quality sample of sufficient quantity that can be banked into aliquots with nearly identical microbial diversity profiles. This collection pipeline is essential to accelerate our understanding of the gut microbiome in health and disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giorgio Casaburi ◽  
Rebbeca M. Duar ◽  
Heather Brown ◽  
Ryan D. Mitchell ◽  
Sufyan Kazi ◽  
...  

AbstractThe gut microbiome plays an important role in early life, protecting newborns from enteric pathogens, promoting immune system development and providing key functions to the infant host. Currently, there are limited data to broadly assess the status of the US healthy infant gut microbiome. To address this gap, we performed a multi-state metagenomic survey and found high levels of bacteria associated with enteric inflammation (e.g. Escherichia, Klebsiella), antibiotic resistance genes, and signatures of dysbiosis, independent of location, age, and diet. Bifidobacterium were less abundant than generally expected and the species identified, including B. breve, B. longum and B. bifidum, had limited genetic capacity to metabolize human milk oligosaccharides (HMOs), while B. infantis strains with a complete capacity for HMOs utilization were found to be exceptionally rare. Considering microbiome composition and functional capacity, this survey revealed a previously unappreciated dysbiosis that is widespread in the contemporary US infant gut microbiome.


Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1113
Author(s):  
Eun-Tae Kim ◽  
Sang-Jin Lee ◽  
Tae-Yong Kim ◽  
Hyo-Gun Lee ◽  
Rahman M. Atikur ◽  
...  

Microbiota plays a critical role in the overall growth performance and health status of dairy cows, especially during their early life. Several studies have reported that fecal microbiome of neonatal calves is shifted by various factors such as diarrhea, antibiotic treatment, or environmental changes. Despite the importance of gut microbiome, a lack of knowledge regarding the composition and functions of microbiota impedes the development of new strategies for improving growth performance and disease resistance during the neonatal calf period. In this study, we utilized next-generation sequencing to monitor the time-dependent dynamics of the gut microbiota of dairy calves before weaning (1–8 weeks of age) and further investigated the microbiome changes caused by diarrhea. Metagenomic analysis revealed that continuous changes, including increasing gut microbiome diversity, occurred from 1 to 5 weeks of age. However, the composition and diversity of the fecal microbiome did not change after 6 weeks of age. The most prominent changes in the fecal microbiome composition caused by aging at family level were a decreased abundance of Bacteroidaceae and Enterobacteriaceae and an increased abundance of Prevotellaceae. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis indicated that the abundance of microbial genes associated with various metabolic pathways changed with aging. All calves with diarrhea symptoms showed drastic microbiome changes and about a week later returned to the microbiome of pre-diarrheal stage regardless of age. At phylum level, abundance of Bacteroidetes was decreased (p = 0.09) and that of Proteobacteria increased (p = 0.07) during diarrhea. PICRUSt analysis indicated that microbial metabolism-related genes, such as starch and sucrose metabolism, sphingolipid metabolism, alanine aspartate, and glutamate metabolism were significantly altered in diarrheal calves. Together, these results highlight the important implications of gut microbiota in gut metabolism and health status of neonatal dairy calves.


2020 ◽  
Author(s):  
Zoe J. Zreloff ◽  
Danielle Lange ◽  
Suzanne D. Vernon ◽  
Martha R. Carlin ◽  
Raul de Jesus Cano

Abstract Background. Inferior quality of biological material compromises data, slows discovery, and wastes research funds. The gut microbiome plays a critical role in human health and disease, yet little attention has been given to optimizing collection and processing methods of human stool. Methods. We collected the entire bowel movement from 2 healthy volunteers: one to examine stool sample heterogeneity and one to test stool sample handling parameters. Sequencing and bioinformatic analyses were used to examine the microbiome composition. Results. The microbiome profile varied depending on where the subsample was obtained from the stool. The exterior cortex of the stool was rich in specific phyla and deficient in others while the interior core of the stool revealed opposite microbiome profiles. Sample processing also resulted in varying microbiome profiles. Homogenization and stabilization at 4°C gave superior microbial diversity profiles compared to the fresh or frozen subsamples of the same stool sample. Bacterial proliferation continued in the fresh subsample when processed at ambient temperature. Bacteroidetes proliferated and Firmicutes diminished during the 30-minute processing of fresh sample. The frozen sample had good overall diversity but Proteobacteria diminished likely because of the freeze/thaw. Conclusions. The microbiome profile is specific to the section of the stool being sampled. Stool sample collection, homogenization, and stabilization at 4°C for 24 hours provides a “neat”, high-quality sample of sufficient quantity that can be banked into aliquots with nearly identical microbial diversity profiles. This collection pipeline is essential to accelerate our understanding of the gut microbiome in health and disease


2020 ◽  
Author(s):  
Changying Zhao ◽  
Ying Wang ◽  
Junjie Yang ◽  
Jiaming Zhang ◽  
Xuemei Liu ◽  
...  

Abstract Background: Vertical microbiome transmission from mothers plays an important role inchildren with the establishment and development of gutmicrobiome.Our previous study has found that gut microbiota dysbiosis is associated with Henoch-Schönleinpurpura(HSP) in children,while it is unclear whether there is a correlation between the gut microbiome of the HSP children and their mothers. Methods: In this study, 50HSP child-mother pairs and 61 matched healthy child-mother pairs were enrolled and examined.Stool samples were collected for DNA extraction and 16S rRNA genesequencing, followed by analyses of the gut microbiota composition.Results: Significant differences were observed in the gut microbiome composition between HSP children and healthy children. Several unique biomarkers, such as Enterococcus, Fusobacterium,Veillonellaand Streptococcus were identified. A significant increase of the relative abundance of Prevotella and Megamonas were observed in HSP’s mothers (HSP-M) compared with mothers of the healthy children (H-M). HSP children’s gut microbiome is closely associated with that of their mothers, and the taxon of AcidaminococcusandRoseburiawere onlyfound in the gut microbiome of HSP children and their mothers (HSP-M+C).Conclusions: Our preliminary study revealed that the gut microbiome of HSP children are closely associated with that of their mothers, although children with HSP still possess unique bacterial biomarkers. Dysbiosis of the maternal gut microbiota may play a critical role in increasing the risk of HSP in children, which deserve further longitudinalinvestigations to uncover its mechanisms.


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