scholarly journals Metabolomic signature of the maternal microbiota in the fetus

2020 ◽  
Author(s):  
Tiina Pessa-Morikawa ◽  
Aleksi Husso ◽  
Olli Kärkkäinen ◽  
Ville Koistinen ◽  
Kati Hanhineva ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Response ◽  
Microbial Metabolites ◽  
Specific Pathogen Free ◽  
Germ Free ◽  
Molecular Features ◽  
Specific Pathogen ◽  
Hydroxyindoleacetic Acid ◽  
Fetal Organs ◽  
Derivatives Of

AbstractThe maternal microbiota affects the development of the offspring by microbial metabolites translocating to the fetus. We investigated samples of placenta, fetal intestine and brain from germ-free (GF) and specific pathogen free (SPF) mouse dams by non-targeted metabolic profiling. One hundred one annotated metabolites and altogether 3680 molecular features were present in significantly different amounts in the placenta and/or fetal organs of GF and SPF mice. The concentrations of more than half of the annotated and differentially expressed metabolites were lower in the GF organs, suggesting their microbial origin or a metabolic response of the host to the presence of gut microbiota. The clearest separation was observed in the placenta. Metabolites that were detected in lower amounts in the fetal organs in the GF mice included 5-aminovaleric acid betaine, trimethylamine N-oxide, catechol-O-sulphate, hippuric and pipecolic acid. Derivatives of the amino acid tryptophan, such as kynurenine, 3-indolepropionic acid and hydroxyindoleacetic acid were also decreased in the absence of microbiota. Several metabolites had higher levels in the GF mice. These could be precursors of microbial metabolites or indicators of host metabolic response to the absence of gut microbiota. 99 molecular features were only detected in the SPF mice, suggesting the existence of yet unidentified microbially modified metabolites that potentially influence fetal development.

scholarly journals Microbiota Facilitates the Formation of the Aminated Metabolite of Tea Polyphenols Which Trap Deleterious Reactive Endogenous Metabolites (P06-022-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shuwei Zhang ◽  
Yantao Zhao ◽  
Christina Ohland ◽  
Christian Jobin ◽  
Shengmin Sang
Keyword(s):  
Gut Microbiota ◽  
Chronic Diseases ◽  
Green Tea ◽  
Tea Polyphenols ◽  
Specific Pathogen Free ◽  
Tea Polyphenol ◽  
Germ Free ◽  
Specific Pathogen ◽  
Conjugated Metabolites

Abstract Objectives The in vivo mechanism of tea polyphenol-mediated prevention of many chronic diseases is still largely unknown. Studies have shown that accumulation of toxic reactive cellular metabolites, such as ammonia and reactive carbonyl species (RCS), is one of the causing factors to the development of many chronic diseases. The objective of this study is to investigated the in vivo interaction between tea polyphenols and ammonia and RCS. Methods In mice, we gave 200 mg/kg tea polyphenol ((-)-epigallocatechin-3-gallate (EGCG) or theaflavin) to CD-1 mice, 129/SvEv specific-pathogen-free (SPF) mice, or germ-free (GF) mice. Urinary and fecal samples were collected in metabolic cages for 24 h. In humans, two healthy volunteers drank 4 cups of Lipton green tea every day for four days. On the fourth day, 24 h urinary and fecal samples were collected after consuming the first cup of tea. Using LC tandem mass, we searched the formation of the aminated and RCS conjugated metabolites of tea polyphenols. Chemical standards were synthesized to confirm the structures of these metabolites. In order to study the impact of gut microbiota on the formation of these metabolites, we also quantified the concentrations of these metabolites in SPF and GF mice. Results We found that both EGCG and theaflavin could rapidly react with ammonia to generate the aminated metabolites. Both tea polyphenols and their aminated metabolites could further scavenge RCS, such as methylglyoxal (MGO), malondialdehyde (MDA), and trans-4-hydroxy-2-nonenal (4-HNE), to produce the RCS conjugates of tea polyphenols and the aminated tea polyphenols. Both the aminated and the RCS conjugated metabolites of EGCG were detected in human after drinking four cups of green tea per day. By comparing the levels of the aminated and the RCS conjugated metabolites in EGCG or theaflavin exposed germ-free (GF) mice and specific-pathogen-free (SPF) mice, we demonstrated that gut microbiota facilitate the formation of the aminated metabolites of tea polyphenols, the RCS conjugates of tea polyphenols, and the RCS conjugates of the aminated tea polyphenols. Conclusions Altogether, this study provides in vivo evidences that tea polyphenols have the capacity to scavenge toxic reactive metabolic wastes. This finding opens a new window to understand the underlying mechanisms by which drinking tea could prevent the development of chronic diseases. Funding Sources We gratefully acknowledge financial support from NIH R01 grant AT008623 to this work.

scholarly journals Mice, Models, Microbiota: How Can We More Accurately Reflect Human Disease?

2021 ◽  
Vol 15 (1) ◽  
pp. 8
Author(s):  
Rahman Ladak ◽  
Dana Philpott
Keyword(s):  
Gut Microbiota ◽  
Translational Research ◽  
Mouse Models ◽  
Human Disease ◽  
Specific Pathogen Free ◽  
Germ Free ◽  
Stage Of Development ◽  
Specific Pathogen

With growing evidence that human disease is affected by the microbiota, many researchers have sought to modulate the microbiomes of mice to improve translational research. Altering their microbiomes, which are usually germ-free or specific pathogen-free, might allow mice to more accurately model human disease and hence produce more applicable findings. However, this has been difficult to apply to individual projects due to the disparity of explained methods and results. In this review, we first describe the immunological functions of the gut microbiota and the methods of altering mice microbiota, from transplantation route to age of transplantation to microbiota source. We then present an approach for how the gut microbiota might be considered when modelling human disease in mice. By organizing findings by type of disease - neurological, immunological, chronic inflammatory, and cancer - we propose that mouse models can be improved by considering the source of the microbiota, the presence or absence of certain microbial phyla, and by timing the transplantation during a physiologically relevant stage of development, such as the first five weeks of life.

scholarly journals Enterococcus Faecium is a Risk Factor for The Outbreak of Anxiety and Depression in Patients With Inflammatory Bowel Disease

2020 ◽  
Author(s):  
Hyo-Min Jang ◽  
Jeon-Kyung Kim ◽  
Min-Kyung Joo ◽  
Yun-Jung Shin ◽  
Kyung-Eon Lee ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Cell Population ◽  
Enterococcus Faecium ◽  
Fecal Microbiota ◽  
Specific Pathogen Free ◽  
Germ Free ◽  
Specific Pathogen ◽  
Inflammatory Bowel ◽  
Anxiety Depression

Abstract BackgroundThe gut microbiota closely communicate with the brain through the microbiota-gut-brain axis. The interaction between gut microbiota may regulate the occurrence of neuropsychiatric disorders, including depression. Therefore, we transplanted the fecal microbiota of patients with inflammatory bowel disease (IBD) or their overpopulated gut bacteria into specific-pathogen-free or germ-free mice and examined their effects regarding the occurrence of colitis and anxiety/depression. ResultsFecal microbiota transplantations (FMTs) from patients with IBD with (/D+) or without depression (/D-) caused IBD-like colitis in the transplanted mice: they increased myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon. FMTs from patients with IBD/D+ caused anxiety-/depression-like behaviors and NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell population and decreased the BDNF+/NeuN+ cell population in the hippocampus. FMTs from patients with IBD/D- caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of microbiota in the feces of patients with IBD (IBD-F) were different from those of healthy-control feces (HC-F). The Enterobacteriaceae and Enterococcaceae populations and fecal lipopolysaccharide levels were higher in IBD-F vs. HC-F. Moreover, the Enterococcaceae population was higher in IBD/D+-F vs. IBD/D--F, while the Bifidobacteria population was lower in IBD/D+-F. FMT from HC alleviated the IBD/D+-F-induced anxiety-/depression-like behaviors and colitis in the transplanted mice. Furthermore, it suppressed IBD/D+-F-induced Enterococcus sp. population in the feces. Enterobacteriaceae Klebsiella oxytoca, Klebsiella pneumoniae, Escherichia coli, and Cronobacter sakazakii abundant in IBD-F, singly or together, caused depression with colitis in germ-free and specific-pathogen-free mice, while Enterococcus faecium abundant in IBD/D+-F did not cause not anxiety/depression and colitis. However, the combination of Enterobacteriaceae with Enterococcus faecium synergistically deteriorated depression and colitis, while its combination with Bifidobacterium longum attenuated them. ConclusionThe interaction between gut microbiota Enterobacteriaceae, Enterococci, and Bifidobacteria may regulate the outbreak of anxiety/depression and IBD through the modulation of NF-κB-involved BDNF expression and gut microbiota. Enterococcus faecium, a probiotic strain, is a risk factor for the outbreak of anxiety/depression in patients with IBD.

The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice

Cephalalgia ◽  
2021 ◽  
pp. 033310242110500
Author(s):  
Li Kang ◽  
Wenjing Tang ◽  
Yaofen Zhang ◽  
Mingjie Zhang ◽  
Jing Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Expression Level ◽  
Specific Pathogen Free ◽  
Trigeminal Nucleus ◽  
Germ Free ◽  
Microbial Profile ◽  
Matched Healthy Control ◽  
Specific Pathogen ◽  
Healthy Control

Background Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. Methods Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. Results In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. Conclusion Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.

scholarly journals Tissue-wide metabolomics reveals wide impact of gut microbiota on mice metabolite composition

2021 ◽  
Author(s):  
Iman Zarei ◽  
Ville M. Koistinen ◽  
Marietta Kokla ◽  
Anton Klåvus ◽  
Ambrin Farizah Babu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Response ◽  
Germ Free ◽  
Molecular Features ◽  
Beneficial Impact ◽  
Health And Disease ◽  
Specific Tissue ◽  
Host Metabolism ◽  
Different Tissues

The essential role of gut microbiota in health and disease is well-recognized, but the biochemical details underling beneficial impact remain largely undefined. Dysbiosis of gut bacteria results in the alteration of certain microbial and host metabolites, and identifying these markers could enhance the early detection of certain diseases. We report LC-MS based non-targeted metabolic profiling to demonstrate a large effect of gut microbiota on mammalian tissue metabolites. It was hypothesized that gut microbiota influences the overall biochemistry of the host metabolome and this effect is tissue-specific. Thirteen different tissues from germ-free and conventional mice were selected and their metabolic differences were analyzed. Our study demonstrated a large effect of the microbiome on mammalian biochemistry at different tissue levels and resulted in significant modulation of metabolites from multiple metabolic pathway (p ≤ 0.05). A vast metabolic response of host to metabolites generated by the microbiota was observed, Hundreds of molecular features were detected exclusively in one mouse group, with the majority of these being unique to specific tissue, suggesting direct impact gut microbiota on host metabolism.

Comparative analysis of microRNA expression profiles in the colons of specific pathogen-free mice and germ-free mice

2021 ◽  
Author(s):  
Ayako Aoki ◽  
Reiji Aoki ◽  
Madoka Yatagai ◽  
Toshiyuki Kawasumi
Keyword(s):  
Gene Ontology ◽  
Comparative Analysis ◽  
Expression Profiles ◽  
Microrna Expression ◽  
Gene Ontology Analysis ◽  
Specific Pathogen Free ◽  
Germ Free ◽  
Mrna Targets ◽  
Significant Gene ◽  
Specific Pathogen

ABSTRACT MicroRNAs play an important role in microbiota–host crosstalk. In this study, we compared microRNA expression in whole colons of specific pathogen-free mice and germ-free mice. Forty-eight microRNAs were differentially expressed by more than 2-fold. Gene ontology analysis of the predicted mRNA targets revealed that the majority of the most significant gene ontology terms were related to GTPases and nerves.

scholarly journals Effects of Breeding Environments on Generation and Activation of Autoreactive B-1 Cells in Anti-red Blood Cell Autoantibody Transgenic Mice

1997 ◽  
Vol 185 (4) ◽  
pp. 791-794 ◽  
Author(s):  
Masao Murakami ◽  
Kazuo Nakajima ◽  
Ken-ichi Yamazaki ◽  
Takehiko Muraguchi ◽  
Tadao Serikawa ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Transgenic Mice ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Bacterial Infections ◽  
Specific Pathogen Free ◽  
Germ Free ◽  
Conventional Condition ◽  
Specific Pathogen ◽  
Almost All

In anti-red blood cell autoantibody transgenic (autoAb Tg) mice almost all B cells are deleted except for B-1 cells in the peritoneal cavity and the gut. About one-half of the auto Ab Tg mice suffer from autoimmune hemolytic anemia (AIHA) in the conventional condition. Oral administration of lipopolysaccharides activates B-1 cells and induces autoimmune symptoms in the Tg mice, suggesting that the autoimmune disease in anti-RBC autoAb Tg mice is triggered by infections. To examine the association of bacterial infections with the generation of B-1 cells and the occurrence of the autoimmune disease, we analyzed anti-RBC autoAb Tg mice bred in germ-free and specific pathogen-free conditions. In germ-free conditions, few peritoneal B-1 cells were detected, while a significant number of peritoneal B-1 cells existed in specific pathogen-free conditions. In both conditions, no mice suffered from AIHA. However, when these Tg mice were transferred to the conventional condition or injected with lipopolysaccharide, peritoneal B-1 cells expanded and some of these mice suffered from AIHA. These results clearly showed that bacterial infections are responsible for both the expansion of B-1 cells and the onset of the autoimmune disease in these Tg mice.

Abstract P241: Intermittent Fasting Lowers Blood Pressure In A Rat Model Of Hypertension By Modulating The Gut Microbiota

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Huanan Shi ◽  
Taylor Abo-Hamzy ◽  
Robert M Bryan ◽  
David J Durgan
Keyword(s):  
Blood Pressure ◽  
Gut Microbiota ◽  
Intermittent Fasting ◽  
Microbial Metabolites ◽  
Targeted Metabolomics ◽  
Oral Gavage ◽  
Spontaneously Hypertensive ◽  
Germ Free ◽  
Wistar Kyoto ◽  
Principle Coordinate Analysis

Studies have demonstrated that disruption of the gut microbiota, termed gut dysbiosis, plays a causal role in the development of hypertension (HT) in animal models and patients. Recent studies revealed that intermittent fasting alters the gut microbiota and the production of microbial metabolites. Thus, we hypothesized that every-other-day-fasting (EODF) would prevent elevations of blood pressure (BP) in spontaneously hypertensive stroke prone rat (SHRSP) by maintaining a healthy gut microbiota. Five-week old SHRSP rats and normotensive Wistar Kyoto (WKY) rats were randomized to be fed ad lib or on EODF for 10 weeks. BP was measured weekly, and cecal content and plasma were collected at the end of the study. To examine the roles of gut microbiota and microbial metabolites in hypertension, we performed whole-genome shotgun sequencing on cecal samples and non-targeted metabolomics on cecal contents and plasma. To examine the direct effects of the EODF altered microbiota on BP regulation and eliminate the confounding variable of fasting, pooled cecal contents of SHRSP and WKY animals fed ad lib or EODF were given to germ free (GF) rats by oral gavage. We found that ten-weeks EODF was able to prevent elevations of systolic BP (SBP) in SHRSP compared to ad lib fed SHRSP (~220 vs. ~170mmHg; n=6-8, p<0.05), and that germ free rats transplanted with SHRSP ad lib microbiota had a significantly higher SBP as compared to those transplanted with SHRSP EODF microbiota (~152 vs. ~140 mmHg; n=6-7, p<0.01), indicating that microbiota and their metabolites are accountable for the effects of EODF. Principle coordinate analysis showed that EODF significantly altered the overall composition of both WKY and SHRSP microbiota (WKY p<0.01, SHRSP p<0.009). Multi-omics analysis indicates distinct microbiome and metabolome in SHRSP compared to WKY, and significant alterations to each induced by EODF. These findings suggest that EODF is able to prevent hypertension in SHRSP, and this involves altering the gut microbiota and metabolome.

Microbial regulation of a lincRNA–miRNA–mRNA network in the mouse hippocampus

Epigenomics ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1377-1387
Author(s):  
Lanxiang Liu ◽  
Haiyang Wang ◽  
Ying Yu ◽  
Benhua Zeng ◽  
Xuechen Rao ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Molecular Basis ◽  
Mapk Signaling ◽  
Specific Pathogen Free ◽  
Rna Transcription ◽  
Germ Free ◽  
Mouse Hippocampus ◽  
Specific Pathogen ◽  
Post Transcriptional Regulation ◽  
Mapk Signaling Pathways

Aim: To comprehensively understand microbiota-regulated lincRNA–miRNA–mRNA networks in psychiatric disorders. Materials & methods: Integrated analyses of lincRNAs, mRNAs and miRNAs, obtained by microarray analysis of hippocampus from specific pathogen-free, germ-free and colonized germ-free mice, were performed. Results: Expression of 139 mRNAs, seven miRNAs and one lincRNA was restored following colonization. The restored transcripts were mainly involved in CREB and Ras/MAPK signaling pathways. RNA transcription and post-transcriptional regulation were the primary perturbed functions. Finally, 12 lincRNAs, six miRNAs and 47 mRNAs were included in a lincRNA–miRNA–mRNA network, and lincRNA0926-miR-190a-5p-Celf4 interactions may play a pivotal role in this regulatory network. Conclusion: This study provides clues for understanding the molecular basis of gut microbiota–brain interactions in depressive- and anxiety-like behaviors.

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