Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

Objective Adult elastic cartilage has limited repair capacity. MRL/MpJ (MRL) mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and non-healer mice and to evaluate whether this healing phenotype can be transferred via gut microbiome transplantation. Methods We orally transplanted C57BL/6J (B6) mice with MRL/MpJ cecal contents at weaning and as adults (n = 57) and measured ear hole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n = 25) and B6-transplanted MRL (n = 20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n = 58), cecal microbiomes were profiled by 16S sequencing and compared to ear hole closure. Microbial metagenomes were imputed using PICRUSt. Results Transplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved ear hole closure. B6-vehicle mice healed ear hole punches poorly (0.25±0.03mm, mm ear hole healing 4 weeks after a 2mm ear hole punch [2.0mm—final ear hole size], mean±SEM), whereas MRL-vehicle mice healed well (1.4±0.1mm). MRL-transplanted B6 mice healed roughly three times as well as B6-vehicle mice, and half as well as MRL-vehicle mice (0.74±0.05mm, P = 6.9E-10 vs. B6-vehicle, P = 5.2E-12 vs. MRL-vehicle). Transplantation of MRL mice with B6 cecal material did not reduce MRL healing (B6-transplanted MRL 1.3±0.1 vs. MRL-vehicle 1.4±0.1, p = 0.36). Transplantation prior to ear punch was associated with the greatest ear hole closure. Offspring of transplanted mice healed significantly better than non-transplanted control mice (offspring:0.63±0.03mm, mean±SEM vs. B6-vehicle control:0.25±0.03mm, n = 39 offspring, P = 4.6E-11). Several microbiome clades were correlated with healing, including Firmicutes (R = 0.84, P = 8.0E-7), Lactobacillales (R = 0.65, P = 1.1E-3), and Verrucomicrobia (R = -0.80, P = 9.2E-6). Females of all groups tended to heal better than males (B6-vehicle P = 0.059, MRL-transplanted B6 P = 0.096, offspring of MRL-transplanted B6 P = 0.0038, B6-transplanted MRL P = 1.6E-6, MRL-vehicle P = 0.0031). Many clades characteristic of female mouse cecal microbiota vs. males were the same as clades characteristic of MRL and MRL-transplanted B6 mice vs. B6 controls, including including increases in Clostridia and reductions in Verrucomicrobia in female mice. Conclusion In this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to non-healer mice via microbiome transplantation. We identified several microbiome clades associated with healing.

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Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

10.1101/2021.02.25.432835 ◽

2021 ◽

Author(s):

Cassandra Velasco ◽

Christopher Dunn ◽

Cassandra Sturdy ◽

Vladislav Izda ◽

Jake Martin ◽

...

Keyword(s):

Tissue Regeneration ◽

Regenerative Therapy ◽

Repair Capacity ◽

Gram Negative ◽

16S Sequencing ◽

Future Studies ◽

Microbiome Composition ◽

Sex Effects ◽

Gram Negative Organisms ◽

Better Than

AbstractObjectiveAdult cartilage has limited repair capacity. MRL/MpJ mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and nonhealer mice and to evaluate microbiome transplantation as a novel regenerative therapy.MethodsWe transplanted C57BL/6J mice with MRL/MpJ cecal contents in mice at weaning and as adults (n=57) and measured earhole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n=25) and B6-transplanted MRL (n=20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n=58), cecal microbiomes were profiled by 16S sequencing and compared to earhole closure rates. Microbial metagenomes were imputed using PICRUSt.ResultsTransplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved earhole closure rates. Transplantation prior to ear punch was associated with the greatest earhole closure. Offspring of transplanted mice healed better than controls. Several microbiome clades were correlated with healing, including Firmicutes, Lactobacillales, and Verrucomicrobia. Gram-negative organisms were reduced. Females of all groups tended to heal better than males, female microbiota resembled MRL mice.ConclusionIn this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to nonhealer mice via microbiome transplantation. We identified several microbiome clades associated with healing. Future studies should evaluate the mechanisms underlying these findings and confirm our results in murine OA.

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Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2016/3876764 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Sandra Mrozinska ◽

Piotr Radkowski ◽

Tomasz Gosiewski ◽

Magdalena Szopa ◽

Malgorzata Bulanda ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gut Microbiome ◽

Bacterial Flora ◽

Control Group ◽

16S Sequencing ◽

Microbiome Composition ◽

Colonic Flora

Background. Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY).Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed.Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher (p=0.0006) and the amount of Bacteroidetes was lower (p=0.0005) in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (p=0.0143). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group.Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.

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Delivery mode and perinatal antibiotics influence the predicted metabolic pathways of the gut microbiome

Scientific Reports ◽

10.1038/s41598-021-97007-x ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Petri Vänni ◽

Mysore V. Tejesvi ◽

Sofia Ainonen ◽

Marjo Renko ◽

Katja Korpela ◽

...

Keyword(s):

Caesarean Section ◽

Gut Microbiome ◽

Biological Effects ◽

Marker Gene ◽

Delivery Mode ◽

16S Sequencing ◽

Microbiome Composition ◽

Carbohydrate Degradation ◽

Functional Profiles ◽

Learning Analysis

AbstractDelivery mode and perinatal antibiotics influence gut microbiome composition in children. Most microbiome studies have used the sequencing of the bacterial 16S marker gene but have not reported the metabolic function of the gut microbiome, which may mediate biological effects on the host. Here, we used the PICRUSt2 bioinformatics tool to predict the functional profiles of the gut microbiome based on 16S sequencing in two child cohorts. Both Caesarean section and perinatal antibiotics markedly influenced the functional profiles of the gut microbiome at the age of 1 year. In machine learning analysis, bacterial fatty acid, phospholipid, and biotin biosynthesis were the most important pathways that differed according to delivery mode. Proteinogenic amino acid biosynthesis, carbohydrate degradation, pyrimidine deoxyribonucleotide and biotin biosynthesis were the most important pathways differing according to antibiotic exposure. Our study shows that both Caesarean section and perinatal antibiotics markedly influence the predicted metabolic profiles of the gut microbiome at the age of 1 year.

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Dysbiosis in dementia is associated with gut barrier dysfunction and linked to malnutrition and prescription drug use

10.21203/rs.2.15653/v1 ◽

2019 ◽

Author(s):

Vanessa Stadlbauer ◽

Lara Engertsberger ◽

Irina Komarova ◽

Nicole Feldbacher ◽

Bettina Leber ◽

...

Keyword(s):

Drug Use ◽

Bacterial Translocation ◽

Gut Microbiome ◽

Short Form ◽

Mini Nutritional Assessment ◽

Gut Permeability ◽

Barrier Dysfunction ◽

Gut Barrier ◽

16S Sequencing ◽

Microbiome Composition

Abstract Background: Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia. Methods: To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16s sequencing, QIIME 2 and Calypso 7.14 tools. Results: Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use use had the strongest impact on microbiome composition.Conclusion: Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Lachnospiraceae NK4A136 group as a potentially butyrate producing bacterial strain was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition and function. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia.Trial Registration: NCT03167983

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Composition of the Gut Microbiome Influences Production of Sulforaphane-Nitrile and Iberin-Nitrile from Glucosinolates in Broccoli Sprouts

Nutrients ◽

10.3390/nu13093013 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3013

Author(s):

John A. Bouranis ◽

Laura M. Beaver ◽

Jaewoo Choi ◽

Carmen P. Wong ◽

Duo Jiang ◽

...

Keyword(s):

Gut Microbiome ◽

Ex Vivo ◽

Human Subjects ◽

Individual Variability ◽

16S Sequencing ◽

Microbiome Composition ◽

Broccoli Sprouts ◽

Broccoli Sprout

Isothiocyanates, such as sulforaphane and iberin, derived from glucosinolates (GLS) in cruciferous vegetables, are known to prevent and suppress cancer development. GLS can also be converted by bacteria to biologically inert nitriles, such as sulforaphane-nitrile (SFN-NIT) and iberin-nitrile (IBN-NIT), but the role of the gut microbiome in this process is relatively undescribed and SFN-NIT excretion in humans is unknown. An ex vivo fecal incubation model with in vitro digested broccoli sprouts and 16S sequencing was utilized to explore the role of the gut microbiome in SFN- and IBN-NIT production. SFN-NIT excretion was measured among human subjects following broccoli sprout consumption. The fecal culture model showed high inter-individual variability in nitrile production and identified two sub-populations of microbial communities among the fecal cultures, which coincided with a differing abundance of nitriles. The Clostridiaceae family was associated with high levels, while individuals with a low abundance of nitriles were more enriched with taxa from the Enterobacteriaceae family. High levels of inter-individual variation in urine SFN-NIT levels were also observed, with peak excretion of SFN-NIT at 24 h post broccoli sprout consumption. These results suggest that nitrile production from broccoli, as opposed to isothiocyanates, could be influenced by gut microbiome composition, potentially lowering efficacy of cruciferous vegetable interventions.

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Long-Term Blackcurrant Supplementation Modified Gut Microbiome Profiles in Mice in an Age-Dependent Manner: An Exploratory Study

Nutrients ◽

10.3390/nu12020290 ◽

2020 ◽

Vol 12 (2) ◽

pp. 290 ◽

Cited By ~ 1

Author(s):

Lei Cao ◽

Sang Gil Lee ◽

Melissa M. Melough ◽

Junichi R. Sakaki ◽

Kendra R. Maas ◽

...

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Age Groups ◽

Dependent Manner ◽

16S Sequencing ◽

Microbiome Composition ◽

Age Related ◽

Regulatory Effects ◽

Old Mice ◽

Young Mice

Recent studies have suggested that blackcurrant (BC) anthocyanins have promising health benefits, possibly through regulating gut microbiome. Three- and eighteen-month old female mice were fed standard mouse diets for 4 months, each with or without BC (1% w/w) supplementation (n = 3 in each treatment group, 12 in total). We then assessed gut microbiome profiles using 16S sequencing of their feces. Old mice had a less diverse microbiome community compared to young mice and there was a remarkable age-related difference in microbiome composition in the beta diversity analysis. BC supplementation did not significantly affect alpha or beta diversity. The relative abundance of several phyla, including Firmicutes, Bacteroidetes, Proteobacteria and Tenericutes, was lower in old mice. BC downregulated Firmicutes abundance in young mice and upregulated Bacteroidetes in both age groups, leading to a decreased Firmicutes/Bacteroidetes ratio. There were age-specific differences in the effect of BC supplementation on the microbiome. Twenty-four operational taxonomic units showed a significant interaction between age and BC supplementation (p < 0.01), which suggests that the ecosystem and the host health status affect the functions and efficiency of BC intake. These results indicate that BC supplementation favorably modulates gut microbiome, but there are distinct age-specific differences. Studies with human hosts are needed to better understand BC’s regulatory effects on the gut microbiome.

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Highly Reproducible 16S Sequencing Facilitates Measurement of Host Genetic Influences on the Stickleback Gut Microbiome

mSystems ◽

10.1128/msystems.00331-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 2

Author(s):

Clayton M. Small ◽

Mark Currey ◽

Emily A. Beck ◽

Susan Bassham ◽

William A. Cresko

Keyword(s):

Microbial Diversity ◽

High Throughput ◽

Gut Microbiome ◽

Dna Isolation ◽

Minor Effect ◽

Tissue Preparation ◽

Host Genotype ◽

16S Sequencing ◽

Microbiome Composition ◽

Host Microbe Interactions

ABSTRACT Multicellular organisms interact with resident microbes in important ways, and a better understanding of host-microbe interactions is aided by tools such as high-throughput 16S sequencing. However, rigorous evaluation of the veracity of these tools in a different context from which they were developed has often lagged behind. Our goal was to perform one such critical test by examining how variation in tissue preparation and DNA isolation could affect inferences about gut microbiome variation between two genetically divergent lines of threespine stickleback fish maintained in the same laboratory environment. Using careful experimental design and intensive sampling of individuals, we addressed technical and biological sources of variation in 16S-based estimates of microbial diversity. After employing a two-tiered bead beating approach that comprised tissue homogenization followed by microbial lysis in subsamples, we found an extremely minor effect of DNA isolation protocol relative to among-host microbial diversity differences. Abundance estimates for rare operational taxonomic units (OTUs), however, showed much lower reproducibility. Gut microbiome composition was highly variable across fish—even among cohoused siblings—relative to technical replicates, but a subtle effect of host genotype (stickleback line) was nevertheless detected for some microbial taxa. IMPORTANCE Our findings demonstrate the importance of appropriately quantifying biological and technical variance components when attempting to understand major influences on high-throughput microbiome data. Our focus was on understanding among-host (biological) variance in community metrics and its magnitude in relation to within-host (technical) variance, because meaningful comparisons among individuals are necessary in addressing major questions in host-microbe ecology and evolution, such as heritability of the microbiome. Our study design and insights should provide a useful example for others desiring to quantify microbiome variation at biological levels in the face of various technical factors in a variety of systems.

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Infant Weight Gain Trajectories Linked to Oral Microbiome Composition

10.1101/208090 ◽

2017 ◽

Author(s):

Sarah J. C. Craig ◽

Daniel Blankenberg ◽

Alice Carla Luisa Parodi ◽

Ian M. Paul ◽

Leann L. Birch ◽

...

Keyword(s):

Weight Gain ◽

Gut Microbiome ◽

Growth Curves ◽

Later Life ◽

Child Growth ◽

Growth Patterns ◽

Oral Microbiome ◽

Rapid Weight Gain ◽

16S Sequencing ◽

Microbiome Composition

ABSTRACTGut and oral microbiome perturbations have been observed in obese adults and adolescents. Less is known about how weight gain in early childhood is influenced by gut, and particularly oral, microbiomes. Here we analyze the relationships among weight gain and gut and oral microbiomes in 226 two-year-olds who were followed during the first two years of life, as part of a larger study, with weight and length measured at seven time points. We used these data to identify children with rapid weight gain (a strong risk factor for childhood obesity), and to derive growth curves with novel Functional Data Analysis (FDA) techniques. The children’s oral and gut microbiomes were sampled at the end of the two-year period, and surveyed with 16S sequencing. First, we show that growth curves are associated negatively with diversity and positively with Firmicutes-to-Bacteroidetes ratio of the oral microbiome – a relationship that is also observed in children with rapid (vs. non-rapid) weight gain. We also demonstrate an association between the gut microbiome and child growth, but only when considering the effect of diet on the microbiome. Lastly, we identify several bacterial genera that are associated with child growth patterns. These results suggest that by the age of two, the oral microbiome may have already begun to establish patterns often seen in older obese individuals. They also suggest that the gut microbiome, while strongly influenced by diet, at age two does not harbor obesity signatures many researchers identified in later life stages.

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0473 - Crowdsourced study of ASD children and their typically developing siblings identifies key differences in gut microbiome composition using ESV analysis

10.26226/morressier.5b5199bfb1b87b000ecee271 ◽

2018 ◽

Author(s):

Maude David

Keyword(s):

Gut Microbiome ◽

Typically Developing ◽

Microbiome Composition ◽

Typically Developing Siblings

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Taxonomic signatures of cause-specific mortality risk in human gut microbiome

Nature Communications ◽

10.1038/s41467-021-22962-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Aaro Salosensaari ◽

Ville Laitinen ◽

Aki S. Havulinna ◽

Guillaume Meric ◽

Susan Cheng ◽

...

Keyword(s):

Mortality Risk ◽

Gut Microbiome ◽

Human Gut ◽

Cross Sectional ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Non Invasive ◽

Sequencing Technologies

AbstractThe collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.

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