Retinitis Pigmentosa is Associated With Shifts in The Gut Microbiome

Abstract The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP). Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retinal degeneration and gut microbiome in the rd10 mouse model of RP as compared to control C57BL/6J mice. In rd10 mice, retinal responsiveness to flashlight stimuli and visual acuity were deteriorated with respect to observed in age-matched control mice. This functional decline in dystrophic animals was accompanied by photoreceptor loss, morphologic anomalies in photoreceptor cells and retinal reactive gliosis. Furthermore, 16S rRNA gene amplicon sequencing data showed a microbial gut dysbiosis with differences in alpha and beta diversity at the genera, species and amplicon sequence variants (ASV) levels between dystrophic and control mice. Remarkably, four fairly common ASV in healthy gut microbiome belonging to Rikenella spp., Muribaculaceace spp., Prevotellaceae UCG-001 spp., and Bacilli spp. were absent in the gut microbiome of retinal disease mice, while Bacteroides caecimuris was significantly enriched in mice with RP. The results indicate that retinal degenerative changes in RP are linked to relevant gut microbiome changes. The findings suggest that microbiome shifting could be considered as potential biomarker and therapeutic target for retinal degenerative diseases.

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Retinitis pigmentosa is associated with shifts in the gut microbiome

Scientific Reports ◽

10.1038/s41598-021-86052-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Oksana Kutsyr ◽

Lucía Maestre-Carballa ◽

Mónica Lluesma-Gomez ◽

Manuel Martinez-Garcia ◽

Nicolás Cuenca ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Gut Microbiome ◽

Functional Decline ◽

Retinal Disease ◽

Photoreceptor Cells ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Sequencing Data ◽

Alpha And Beta Diversity ◽

Potential Biomarker

AbstractThe gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP). Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retinal degeneration and gut microbiome in the rd10 mouse model of RP as compared to control C57BL/6J mice. In rd10 mice, retinal responsiveness to flashlight stimuli and visual acuity were deteriorated with respect to observed in age-matched control mice. This functional decline in dystrophic animals was accompanied by photoreceptor loss, morphologic anomalies in photoreceptor cells and retinal reactive gliosis. Furthermore, 16S rRNA gene amplicon sequencing data showed a microbial gut dysbiosis with differences in alpha and beta diversity at the genera, species and amplicon sequence variants (ASV) levels between dystrophic and control mice. Remarkably, four fairly common ASV in healthy gut microbiome belonging to Rikenella spp., Muribaculaceace spp., Prevotellaceae UCG-001 spp., and Bacilli spp. were absent in the gut microbiome of retinal disease mice, while Bacteroides caecimuris was significantly enriched in mice with RP. The results indicate that retinal degenerative changes in RP are linked to relevant gut microbiome changes. The findings suggest that microbiome shifting could be considered as potential biomarker and therapeutic target for retinal degenerative diseases.

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Retinitis Pigmentosa Is Associated With Shifts in The Gut Microbiome

10.21203/rs.3.rs-107256/v1 ◽

2020 ◽

Author(s):

Oksana Kutsyr ◽

Lucía Maestre-Carballa ◽

Mónica Lluesma-Gomez ◽

Manuel Martinez-Garcia ◽

Nicolás Cuenca ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Gut Microbiome ◽

Outer Nuclear Layer ◽

Functional Decline ◽

Retinal Disease ◽

Rrna Gene ◽

Sequencing Data ◽

Cell Reactivity ◽

Alpha And Beta Diversity ◽

Potential Biomarker

Abstract Background: The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP) that leads to photoreceptor degeneration and is the main worldwide cause of complete blindness in adulthood. Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retinal degeneration and gut microbiome in the rd10 mouse model of RP as compared to control C57BL/6J mice.Results: In rd10 mice, retinal responsiveness to flashlight stimuli was deteriorated with respect to observed in age-matched control mice, with decreased amplitudes in the a- and b-wave responses of the electroretinogram and concomitant reduction of the visual acuity. This functional decline in dystrophic animals was accompanied by photoreceptor loss, evidenced by decreased outer nuclear layer thickness, and morphologic anomalies in photoreceptor cells. Changes in retinal neurons were paralleled to induction of reactive gliosis in retina, with increased microglial cell numbers and higher Müller cell reactivity in rd10 mice. Furthermore, 16S rRNA gene amplicon sequencing data showed a microbial gut dysbiosis with differences in alpha and beta diversity at the genera, species and amplicon sequence variants (ASV) levels between dystrophic and control mice. A taxonomic partitioning of ASV was observed since unique ASVs present in only one group had a cumulative relative microbial abundance between 17.6% (rd10 mice) and 26.7% (C57BL/6J mice). Remarkably, four fairly common ASV in healthy gut microbiome belonging to -Rikenella spp., Muribaculaceace spp., Prevotellaceae UCG-001 spp., and Bacilli spp.- were absent in the gut microbiome of retinal disease mice, while Bacteroides caecimuris was significantly enriched in mice with retinitis pigmentosa. Conclusions: Our results indicate that retinal degenerative changes in retinitis pigmentosa are linked to relevant gut microbiome changes. The findings suggest that microbiome shifting could be considered as potential biomarker and therapeutic target for retinal degenerative diseases.

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Insights into the Potential of the Atlantic Cod Gut Microbiome as Biomarker of Oil Contamination in the Marine Environment

Microorganisms ◽

10.3390/microorganisms7070209 ◽

2019 ◽

Vol 7 (7) ◽

pp. 209 ◽

Cited By ~ 7

Author(s):

Juline M. Walter ◽

Andrea Bagi ◽

Daniela M. Pampanin

Keyword(s):

Gut Microbiota ◽

Marine Environment ◽

Gut Microbiome ◽

Atlantic Cod ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Sequencing Data ◽

Comparison Results ◽

Southern Norway ◽

Microbial Groups

Background: Microorganisms are widespread in all environments, including in and on animal bodies. The gut microbiome has an essential influence on fish health, and is affected by several persistent and harmful organic and inorganic contaminants. Considering the shifts in gut microbiota composition observed in those studies, we hypothesized that certain microbial groups in the gut can serve as indicators of pollution. To test this hypothesis, we explored the possibility of identifying key microbial players that indicate environmental contamination. Methods: Published 16S rRNA gene amplicon sequencing data generated from the gut microbiota of Atlantic cod caught in geographically different Norwegian waters were used for bacterial diversity comparison. Results: Different microbiomes were identified between the northern Norway and southern Norway samples. Several bacterial genera previously identified as polycyclic aromatic hydrocarbon degraders were present only in the samples collected in the southern Norway area, suggesting fish contamination with oil-related compounds. Conclusions: The results contribute to the identification of bacterial taxa present in the Atlantic cod gut that indicate fish exposure to contaminants in the marine environment.

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Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity

Genome Biology ◽

10.1186/s13059-019-1831-z ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 14

Author(s):

Robert C. Kaplan ◽

Zheng Wang ◽

Mykhaylo Usyk ◽

Daniela Sotres-Alvarez ◽

Martha L. Daviglus ◽

...

Keyword(s):

Community Health ◽

Gut Microbiome ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Shannon Index ◽

Health Study ◽

Rrna Gene ◽

Cross Sectional ◽

Hispanic Community ◽

The Usa

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

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Culture-Independent and Culture-Dependent Characterization of the Black Soldier Fly Gut Microbiome Reveals a Large Proportion of Culturable Bacteria with Potential for Industrial Applications

Microorganisms ◽

10.3390/microorganisms9081642 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1642

Author(s):

Dorothee Tegtmeier ◽

Sabine Hurka ◽

Sanja Mihajlovic ◽

Maren Bodenschatz ◽

Stephanie Schlimbach ◽

...

Keyword(s):

Gut Microbiome ◽

Amplicon Sequencing ◽

Industrial Applications ◽

Culture Collection ◽

Rrna Gene ◽

Organic Substrates ◽

Culturable Bacteria ◽

Black Soldier Fly ◽

Culture Independent ◽

Culture Dependent

Black soldier fly larvae (BSFL) are fast-growing, resilient insects that can break down a variety of organic substrates and convert them into valuable proteins and lipids for applications in the feed industry. Decomposition is mediated by an abundant and versatile gut microbiome, which has been studied for more than a decade. However, little is known about the phylogeny, properties and functions of bacterial isolates from the BSFL gut. We therefore characterized the BSFL gut microbiome in detail, evaluating bacterial diversity by culture-dependent methods and amplicon sequencing of the 16S rRNA gene. Redundant strains were identified by genomic fingerprinting and 105 non-redundant isolates were then tested for their ability to inhibit pathogens. We cultivated representatives of 26 genera, covering 47% of the families and 33% of the genera detected by amplicon sequencing. Among these isolates, we found several representatives of the most abundant genera: Morganella, Enterococcus, Proteus and Providencia. We also isolated diverse members of the less-abundant phylum Actinobacteria, and a novel genus of the order Clostridiales. We found that 15 of the isolates inhibited at least one of the tested pathogens, suggesting a role in helping to prevent colonization by pathogens in the gut. The resulting culture collection of unique BSFL gut bacteria provides a promising resource for multiple industrial applications.

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Yoghurt Consumption is Associated With Transient Changes in the Composition of the Human Gut Microbiome

10.21203/rs.3.rs-99718/v1 ◽

2020 ◽

Author(s):

Caroline Ivanne Le Roy ◽

Alexander Kurilshikov ◽

Emily Leeming ◽

Alessia Visconti ◽

Ruth Bowyer ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

Visceral Fat ◽

Gut Microbiome ◽

Body Weight Gain ◽

Healthy Eating Index ◽

Rrna Gene ◽

Metagenomic Sequencing ◽

Sequencing Data ◽

Shotgun Metagenomic Sequencing

Abstract Background: Yoghurt contains live bacteria that could contribute via modulation of the gut microbiota to its reported beneficial effects such as reduced body weight gain and lower incidence of type 2 diabetes. To date, the association between yoghurt consumption and the composition of the gut microbiota is underexplored. Here we used clinical variables, metabolomics, 16S rRNA and shotgun metagenomic sequencing data collected on over 1000 predominantly female UK twins to define the link between the gut microbiota and yoghurt-associated health benefits. Results: According to food frequency questionnaires (FFQ), 73% of subjects consumed yoghurt. Consumers presented a healthier diet pattern (healthy eating index: beta = 2.17±0.34; P = 2.72x10-10) and improved metabolic health characterised by reduced visceral fat (beta = -28.18±11.71 g; P = 0.01). According to 16S rRNA gene analyses and whole shotgun metagenomic sequencing approach consistent taxonomic variations were observed with yoghurt consumption. More specifically, we identified higher abundance of species used as yoghurt starters Streptococcus thermophilus (beta = 0.41±0.051; P = 6.14x10-12) and sometimes added Bifidobacterium animalis subsp. lactis (beta = 0.30±0.052; P = 1.49x10-8) in the gut of yoghurt consumers. Replication in 1103 volunteers from the LifeLines-DEEP cohort confirmed the increase of S. thermophilus among yoghurt consumers. Using food records collected the day prior to faecal sampling we showed that increase in these two yoghurt bacteria could be transient. Metabolomics analysis revealed that B. animalis subsp. lactis was associated with 13 faecal metabolites including a 3-hydroxyoctanoic acid, known to be involved in the regulation of gut inflammation.Conclusions: Yoghurt consumption is associated with reduced visceral fat mass and changes in gut microbiome including transient increase of yoghurt-contained species (i.e. S. thermophilus and B. lactis).

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Gut microbiota composition is associated with narcolepsy type 1

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000896 ◽

2020 ◽

Vol 7 (6) ◽

pp. e896

Author(s):

Alexandre Lecomte ◽

Lucie Barateau ◽

Pedro Pereira ◽

Lars Paulin ◽

Petri Auvinen ◽

...

Keyword(s):

Community Structure ◽

Gut Microbiota ◽

Bacterial Communities ◽

Beta Diversity ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Differential Abundance ◽

Alpha And Beta Diversity

ObjectiveTo test the hypothesis that narcolepsy type 1 (NT1) is related to the gut microbiota, we compared the microbiota bacterial communities of patients with NT1 and control subjects.MethodsThirty-five patients with NT1 (51.43% women, mean age 38.29 ± 19.98 years) and 41 controls (57.14% women, mean age 36.14 ± 12.68 years) were included. Stool samples were collected, and the fecal microbiota bacterial communities were compared between patients and controls using the well-standardized 16S rRNA gene amplicon sequencing approach. We studied alpha and beta diversity and differential abundance analysis between patients and controls, and between subgroups of patients with NT1.ResultsWe found no between-group differences for alpha diversity, but we discovered in NT1 a link with NT1 disease duration. We highlighted differences in the global bacterial community structure as assessed by beta diversity metrics even after adjustments for potential confounders as body mass index (BMI), often increased in NT1. Our results revealed differential abundance of several operational taxonomic units within Bacteroidetes, Bacteroides, and Flavonifractor between patients and controls, but not after adjusting for BMI.ConclusionWe provide evidence of gut microbial community structure alterations in NT1. However, further larger and longitudinal multiomics studies are required to replicate and elucidate the relationship between the gut microbiota, immunity dysregulation and NT1.

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A LINE-1 insertion situated in the promoter of IMPG2 is associated with autosomal recessive progressive retinal atrophy in Lhasa Apso dogs

BMC Genetics ◽

10.1186/s12863-020-00911-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Rebekkah J. Hitti-Malin ◽

Louise M. Burmeister ◽

Sally L. Ricketts ◽

Thomas W. Lewis ◽

Louise Pettitt ◽

...

Keyword(s):

Genome Wide Association Study ◽

Retinal Disease ◽

Photoreceptor Cells ◽

Causal Variant ◽

Sequencing Analysis ◽

Sequencing Data ◽

Progressive Retinal Atrophy ◽

Dna Test ◽

A Genome ◽

The Uk

Abstract Background Canine progressive retinal atrophies are a group of hereditary retinal degenerations in dogs characterised by depletion of photoreceptor cells in the retina, which ultimately leads to blindness. PRA in the Lhasa Apso (LA) dog has not previously been clinically characterised or described in the literature, but owners in the UK are advised to have their dog examined through the British Veterinary Association/ Kennel Club/ International Sheep Dog Society (BVA/KC/ISDS) eye scheme annually, and similar schemes that are in operation in other countries. After the exclusion of 25 previously reported canine retinal mutations in LA PRA-affected dogs, we sought to identify the genetic cause of PRA in this breed. Results Analysis of whole-exome sequencing data of three PRA-affected LA and three LA without signs of PRA did not identify any exonic or splice site variants, suggesting the causal variant was non-exonic. We subsequently undertook a genome-wide association study (GWAS), which identified a 1.3 Mb disease-associated region on canine chromosome 33, followed by whole-genome sequencing analysis that revealed a long interspersed element-1 (LINE-1) insertion upstream of the IMPG2 gene. IMPG2 has previously been implicated in human retinal disease; however, until now no canine PRAs have been associated with this gene. The identification of this PRA-associated variant has enabled the development of a DNA test for this form of PRA in the breed, here termed PRA4 to distinguish it from other forms of PRA described in other breeds. This test has been used to determine the genotypes of over 900 LA dogs. A large cohort of genotyped dogs was used to estimate the allele frequency as between 0.07–0.1 in the UK LA population. Conclusions Through the use of GWAS and subsequent sequencing of a PRA case, we have identified a LINE-1 insertion in the retinal candidate gene IMPG2 that is associated with a form of PRA in the LA dog. Validation of this variant in 447 dogs of 123 breeds determined it was private to LA dogs. We envisage that, over time, the developed DNA test will offer breeders the opportunity to avoid producing dogs affected with this form of PRA.

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Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

Genes ◽

10.3390/genes10100748 ◽

2019 ◽

Vol 10 (10) ◽

pp. 748 ◽

Cited By ~ 5

Author(s):

Jin-Young Lee ◽

Mohamed Mannaa ◽

Yunkyung Kim ◽

Jehun Kim ◽

Geun-Tae Kim ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Bacterial Species ◽

Amplicon Sequencing ◽

Fecal Microbiota ◽

Rrna Gene ◽

Microbiota Composition ◽

Stool Samples ◽

Gut Microbiota Composition

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.

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Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome

Frontiers in Physiology ◽

10.3389/fphys.2021.663950 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jin Xue ◽

Celeste Allaband ◽

Dan Zhou ◽

Orit Poulsen ◽

Cameron Martino ◽

...

Keyword(s):

Gut Microbiome ◽

Intermittent Hypoxia ◽

Amplicon Sequencing ◽

Rrna Gene ◽

Atherosclerosis Progression ◽

Atherosclerotic Lesions ◽

Obstructive Sleep ◽

Atherosclerosis Risk ◽

Vascular Beds ◽

Deficient Mice

Obstructive sleep apnea (OSA), a common sleep disorder characterized by intermittent hypoxia and hypercapnia (IHC), increases atherosclerosis risk. However, the contribution of intermittent hypoxia (IH) or intermittent hypercapnia (IC) in promoting atherosclerosis remains unclear. Since gut microbiota and metabolites have been implicated in atherosclerosis, we examined whether IH or IC alters the microbiome and metabolome to induce a pro-atherosclerotic state. Apolipoprotein E deficient mice (ApoE−/−), treated with IH or IC on a high-fat diet (HFD) for 10 weeks, were compared to Air controls. Atherosclerotic lesions were examined, gut microbiome was profiled using 16S rRNA gene amplicon sequencing and metabolome was assessed by untargeted mass spectrometry. In the aorta, IC-induced atherosclerosis was significantly greater than IH and Air controls (aorta, IC 11.1 ± 0.7% vs. IH 7.6 ± 0.4%, p < 0.05 vs. Air 8.1 ± 0.8%, p < 0.05). In the pulmonary artery (PA), however, IH, IC, and Air were significantly different from each other in atherosclerotic formation with the largest lesion observed under IH (PA, IH 40.9 ± 2.0% vs. IC 20.1 ± 2.6% vs. Air 12.2 ± 1.5%, p < 0.05). The most differentially abundant microbial families (p < 0.001) were Peptostreptococcaceae, Ruminococcaceae, and Erysipelotrichaceae. The most differentially abundant metabolites (p < 0.001) were tauro-β-muricholic acid, ursodeoxycholic acid, and lysophosphoethanolamine (18:0). We conclude that IH and IC (a) modulate atherosclerosis progression differently in distinct vascular beds with IC, unlike IH, facilitating atherosclerosis in both aorta and PA and (b) promote an atherosclerotic luminal gut environment that is more evident in IH than IC. We speculate that the resulting changes in the gut metabolome and microbiome interact differently with distinct vascular beds.

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