Thymol and Carvacrol Affect Hybrid Tilapia through the Combination of Direct Stimulation and an Intestinal Microbiota-Mediated Effect: Insights from a Germ-Free Zebrafish Model

Abstract Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.

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Role of the intestinal microbiota in the activation of the promutagen 2,6-dinitrotoluene to mutagenic urine metabolites and comparison of GI enzyme activities in germ-free and conventionalized male Fischer 344 rats

Cancer Letters ◽

10.1016/0304-3835(94)90258-5 ◽

1994 ◽

Vol 79 (2) ◽

pp. 181-187 ◽

Cited By ~ 5

Author(s):

S.Elizabeth George ◽

Robert W. Chadwick ◽

Michael J. Kohan ◽

Joyce C. Allison ◽

Ron W. Williams ◽

...

Keyword(s):

Intestinal Microbiota ◽

Enzyme Activities ◽

Fischer 344 Rats ◽

Urine Metabolites ◽

Germ Free ◽

Fischer 344

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Tributyltin exposure leads to increased adiposity and reduced abundance of leptogenic bacteria in the zebrafish intestine

10.1101/2021.07.09.451869 ◽

2021 ◽

Author(s):

Sol Gomez de la Torre Canny ◽

Olaf Mueller ◽

Camil V Craciunescu ◽

Bruce Blumberg ◽

John F. Rawls

Keyword(s):

Adipose Tissue ◽

Intestinal Microbiota ◽

Direct Action ◽

Microbiota Composition ◽

Bacterial Strains ◽

Fat Storage ◽

Germ Free ◽

Reciprocal Interactions ◽

Reduced Body

The chemical obesogen tributyltin (TBT) is known to promote fat storage in adipose tissue through direct action on vertebrate cells. TBT also has direct toxic effects on microorganisms, raising the possibility that TBT may also promote fat storage in vertebrates by altering their microbiota. Here we show that exposure of conventionally-reared post-embryonic zebrafish to TBT results in increased adiposity, reduced body size, and altered intestinal microbiota composition including reduced relative abundance of Plesiomonas bacteria. To test if those microbiota alterations affected host adiposity, we exposed conventionally-reared zebrafish to intestinal bacterial strains representative of TBT-altered taxa. We found that introduction of a Plesiomonas strain into conventionally-reared zebrafish was sufficient to reduce adiposity and alter intestinal microbiota composition. Using new long-term gnotobiotic zebrafish husbandry methods, we found that colonization of germ-free zebrafish with Plesiomonas was sufficient to reduce host adiposity. These findings underscore how complex reciprocal interactions between animals and their microbial and chemical environments can influence energy balance and metabolic health.

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Milk sialyllactose influences colitis in mice through selective intestinal bacterial colonization

Journal of Experimental Medicine ◽

10.1084/jem.20101098 ◽

2010 ◽

Vol 207 (13) ◽

pp. 2843-2854 ◽

Cited By ~ 71

Author(s):

Andrea Fuhrer ◽

Norbert Sprenger ◽

Ekaterina Kurakevich ◽

Lubor Borsig ◽

Christophe Chassard ◽

...

Keyword(s):

Intestinal Microbiota ◽

Bacterial Colonization ◽

Milk Analysis ◽

Milk Oligosaccharides ◽

Newborn Mice ◽

Germ Free ◽

Adult Mice ◽

Decoy Receptors ◽

Colonization Patterns ◽

Leukocyte Populations

Milk oligosaccharides contribute to the development of the intestinal environment by acting as decoy receptors for pathogens and as prebiotics, which promote the colonization of commensal bacteria. Here, using α2,3- and α2,6-sialyltransferase-deficient mice, we investigated the role of the sialylated milk oligosaccharides sialyl(α2,3)lactose and sialyl(α2,6)lactose on mucosal immunity. The exposure of newborn mice to milk containing or deficient in sialyllactose had no impact on the development of mucosal leukocyte populations. However, when challenged by dextran sulfate sodium (DSS) in drinking water, adult mice that had been fostered on sialyl(α2,3)lactose-deficient milk were more resistant to colitis compared with mice fostered on normal milk or sialyl(α2,6)lactose-deficient milk. Analysis of intestinal microbiota showed different colonization patterns depending on the presence or absence of sialyl(α2,3)lactose in the milk. Germ-free mice reconstituted with intestinal microbiota isolated from mice fed on sialyl(α2,3)lactose-deficient milk were more resistant to DSS-induced colitis than germ-free mice reconstituted with standard intestinal microbiota. Thus, exposure to sialyllactose during infancy affects bacterial colonization of the intestine, which influences the susceptibility to DSS-induced colitis in adult mice.

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Association of germ-free mice with a simplified human intestinal microbiota results in a shortened intestine

Gut Microbes ◽

10.4161/gmic.28203 ◽

2014 ◽

Vol 5 (2) ◽

pp. 176-182 ◽

Cited By ~ 10

Author(s):

Kathleen Slezak ◽

Zuzana Krupova ◽

Sylvie Rabot ◽

Gunnar Loh ◽

Florence Levenez ◽

...

Keyword(s):

Intestinal Microbiota ◽

Germ Free ◽

Human Intestinal Microbiota

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Gut-derived Metabolites Influence Neurodevelopmental Gene Expression and Wnt Signalling Events in a Germ-free Zebrafish Model

10.21203/rs.3.rs-1250656/v1 ◽

2022 ◽

Author(s):

Terry Van Raay ◽

Victoria Rea ◽

Ian Bell

Keyword(s):

Gene Expression ◽

Neural Development ◽

Morphological Changes ◽

Wnt Signalling ◽

Gene Ontology Analysis ◽

Rna Seq ◽

Zebrafish Model ◽

Germ Free ◽

The Impact ◽

The Brain

Abstract Background : Small molecule metabolites produced by the microbiome are known to be neuroactive and are capable of directly impacting the brain and central nervous system, yet there is little data on the contribution of these metabolites to the earliest stages of neural development and neural gene expression. Here, we explore the impact of deriving zebrafish embryos in the absence of microbes on early neural development as well as investigate whether any potential changes can be rescued with treatment of metabolites derived from the zebrafish gut microbiota. Results : Overall, we did not observe any gross morphological changes between treatments but did observe a significant decrease in neural gene expression in embryos raised germ-free, which was rescued with the addition of zebrafish metabolites. Specifically, we identified 354 genes significantly down regulated in germ-free embryos compared to conventionally raised embryos via RNA-Seq analysis. Of these, 42 were rescued with a single treatment of zebrafish gut-derived metabolites to germ-free embryos. Gene ontology analysis revealed that these genes are involved in prominent neurodevelopmental pathways including transcriptional regulation and Wnt signalling. Consistent with the ontology analysis, we found alterations in the development of Wnt dependent events which was rescued in the germ-free embryos treated with metabolites. Conclusions : These findings demonstrate that gut-derived metabolites are in part responsible for regulating critical signalling pathways in the brain, especially during neural development.

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Gut-derived metabolites influence neurodevelopmental gene expression and Wnt signalling events in a germ-free zebrafish model

10.1101/2021.07.06.451297 ◽

2021 ◽

Author(s):

Victoria Rea ◽

Ian Bell ◽

Terence J Van Raay

Keyword(s):

Gene Expression ◽

Neural Development ◽

Morphological Changes ◽

Wnt Signalling ◽

Gene Ontology Analysis ◽

Rna Seq ◽

Zebrafish Model ◽

Germ Free ◽

The Impact ◽

The Brain

Small molecule metabolites produced by the microbiome are known to be neuroactive and are capable of directly impacting the brain and central nervous system, yet there is little data on the contribution of these metabolites to the earliest stages of neural development and neural gene expression. Here, we explore the impact of rearing zebrafish embryos in the absence of microbes on early neural development as well as investigate whether any potential changes can be rescued with treatment of metabolites derived from the zebrafish gut microbiota. Overall, we did not observe any gross morphological changes between treatments but did observe a significant decrease in neural gene expression in embryos raised germ-free, which was rescued with the addition of zebrafish metabolites. Specifically, we identified 361 genes significantly down regulated in GF embryos compared to conventionally raised embryos via RNA-Seq analysis. Of these, 42 were rescued with the treatment of zebrafish gut-derived metabolites to GF embryos. Gene ontology analysis revealed that these genes are involved in prominent neurodevelopmental pathways including transcriptional regulation and Wnt signalling. Consistent with the ontology analysis, we found alterations in the development of Wnt dependent events which is rescued in the GF embryos treated with metabolites.

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Effect of gut microbiota from Henoch-Schönlein Purpura patients on acid-sensitive ion channel 3 expression and intestinal motility in germ-free rats

BMC Pediatrics ◽

10.1186/s12887-021-03013-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jin-kun Wang ◽

Bo Yan ◽

Jun-mei Zhao ◽

Li-ping Yuan

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Motility ◽

Fecal Microbiota ◽

Control Group ◽

Healthy Children ◽

Visceral Sensitivity ◽

Henoch Schonlein Purpura ◽

Germ Free ◽

Schonlein Purpura

Abstract Background It has been proven that gut microbiota alterations are involved in the development of Henoch-Schönlein Purpura (HSP). However, the pathogenesis of HSP hasn’t been eluciated. This study was to investigate the impact of gut microbiota from HSP on ASIC3 expression and interactions between microbiota and ASIC3 expression in the development of HSP. Methods Feces collected from HSP and healthy children at the First Affiliated Hospital of Anhui Medical University were made into fecal microbial solutions. Germ-free rats were randomly assigned to either the control or HSP groups. The HSP group of rats were administered the fecal microbiota solution of HSP children, while the control group rats were administered the fecal microbiota solution of healthy children. Abdominal withdrawal reflex (AWR) and intestinal propulsion rate of the rats were used to determine visceral sensitivity. Composition of the gut microbiota of HSP children was determined using 16S rRNA gene sequencing. ASIC3 expression in the colon was ascertained through qRT-PCR as well as western blotting analysis. Results The results showed a reduction in the number of species and abundance in the intestinal microbiota of children with HSP. Visceral sensitivity and intestinal propulsion rate of HSP group rats increased significantly, compared with the control group. Colon ASIC3 mRNA and protein levels in the HSP group were found to be upregulated. The microbiota dysbiosis of HSP patients could stimulate ASIC3 expression in the colon of Germ-free rats, which in turn affected intestinal motility. Conclusions These results suggested that HSP children had intestinal microbiota disorder, which might affect gut motility by down-regulating colon ASIC3 expression in rats.

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The Absence of Gut Microbiota Alters the Development of the Apicomplexan Parasite Eimeria tenella

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.632556 ◽

2021 ◽

Vol 10 ◽

Author(s):

Pauline Gaboriaud ◽

Guillaume Sadrin ◽

Edouard Guitton ◽

Geneviève Fort ◽

Alisson Niepceron ◽

...

Keyword(s):

Intestinal Microbiota ◽

Second Generation ◽

Histological Analysis ◽

Negative Impact ◽

Parasite Load ◽

Eimeria Tenella ◽

Gene Expressions ◽

Germ Free ◽

The Impact

Coccidiosis is a widespread intestinal disease of poultry caused by a parasite of the genus Eimeria. Eimeria tenella, is one of the most virulent species that specifically colonizes the caeca, an organ which harbors a rich and complex microbiota. Our objective was to study the impact of the intestinal microbiota on parasite infection and development using an original model of germ-free broilers. We observed that germ-free chickens presented significantly much lower load of oocysts in caecal contents than conventional chickens. This decrease in parasite load was measurable in caecal tissue by RT-qPCR at early time points. Histological analysis revealed the presence of much less first (day 2pi) and second generation schizonts (day 3.5pi) in germ-free chickens than conventional chickens. Indeed, at day 3.5pi, second generation schizonts were respectively immature only in germ-free chickens suggesting a lengthening of the asexual phase of the parasite in the absence of microbiota. Accordingly to the consequence of this lengthening, a delay in specific gamete gene expressions, and a reduction of gamete detection by histological analysis in caeca of germ-free chickens were observed. These differences in parasite load might result from an initial reduction of the excystation efficiency of the parasite in the gut of germ-free chickens. However, as bile salts involved in the excystation step led to an even higher excystation efficiency in germ-free compared to conventional chickens, this result could not explain the difference in parasite load. Interestingly, when we shunted the excystation step in vivo by infecting chickens with sporozoites using the cloacal route of inoculation, parasite invasion was similar in germ-free and in conventional chickens but still resulted in significantly lower parasite load in germ-free chickens at day 7pi. Overall, these data highlighted that the absence of intestinal microbiota alters E. tenella replication. Strategies to modulate the microbiota and/or its metabolites could therefore be an alternative approach to limit the negative impact of coccidiosis in poultry.

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