scholarly journals Gut microbiome affects the metabolism of metronidazole in mice through regulation of hepatic cytochromes P450 expression

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259643
Author(s):  
Nina Zemanová ◽  
Kateřina Lněničková ◽  
Markéta Vavrečková ◽  
Eva Anzenbacherová ◽  
Pavel Anzenbacher ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Gut Microbiota ◽  
Mrna Expression ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Cytochromes P450 ◽  
Parent Drug ◽  
Metabolizing Enzymes ◽  
Biotransformation Enzymes ◽  
Specific Pathogen

Microbiome is now considered as a significant metabolic organ with an immense potential to influence overall human health. A number of diseases that are associated with pharmacotherapy interventions was linked with altered gut microbiota. Moreover, it has been reported earlier that gut microbiome modulates the fate of more than 30 commonly used drugs and, vice versa, drugs have been shown to affect the composition of the gut microbiome. The molecular mechanisms of this mutual relationship, however, remain mostly elusive. Recent studies indicate an indirect effect of the gut microbiome through its metabolites on the expression of biotransformation enzymes in the liver. The aim of this study was to analyse the effect of gut microbiome on the fate of metronidazole in the mice through modulation of system of drug metabolizing enzymes, namely by alteration of the expression and activity of selected cytochromes P450 (CYPs). To assess the influence of gut microbiome, germ-free mice (GF) in comparison to control specific-pathogen-free (SPF) mice were used. First, it has been found that the absence of microbiota significantly affected plasma concentration of metronidazole, resulting in higher levels (by 30%) of the parent drug in murine plasma of GF mice. Further, the significant interaction between presence/absence of the gut microbiome and effect of metronidazole application, which together influence mRNA expression of CAR, PPARα, Cyp2b10 and Cyp2c38 was determined. Administration of metronidazole itself influenced significantly mRNA expression of Cyp1a2, Cyp2b10, Cyp2c38 and Cyp2d22. Finally, GF mice have shown lower level of enzyme activity of CYP2A and CYP3A than their SPF counterparts. The results hence have shown that, beside direct bacterial metabolism, different expression and enzyme activity of hepatic CYPs in the presence/absence of gut microbiota may be responsible for the altered metronidazole metabolism.

scholarly journals Presence or absence of microbiome modulates the response of mice organism to administered drug nabumetone

2020 ◽  
pp. 583-594
Author(s):  
L Jourová ◽  
B Lišková ◽  
K Lněničková ◽  
N Zemanová ◽  
P Anzenbacher ◽  
...  
Keyword(s):  
Small Intestine ◽  
Molecular Mechanisms ◽  
Cytochromes P450 ◽  
Active Form ◽  
Drug Metabolizing Enzymes ◽  
Specific Pathogen Free ◽  
Metabolizing Enzymes ◽  
Germ Free ◽  
Wide Range ◽  
Specific Pathogen

The gut microbiota provides a wide range of beneficial functions for the host, and has an immense effect on the host’s health status. The presence of microbiome in the gut may often influence the effect of an orally administered drug. Molecular mechanisms of this process are however mostly unclear. We investigated how the effect of a nonsteroidal drug nabumetone on expression of drug metabolizing enzymes (DMEs) in mice intestine and liver is changed by the presence of microbiota, here, using the germ free (GF) and specific pathogen free (SPF) BALB/c mice. First, we have found in a preliminary experiment that in the GF mice there is a tendency to increase bioavailability of the active form of nabumetone, which we have found now to be possibly influenced by differences in expression of DMEs in the GF and SPF mice. Indeed, we have observed that the expression of the most of selected cytochromes P450 (CYPs) was significantly changed in the small intestine of GF mice compared to the SPF ones. Moreover, orally administered nabumetone itself altered the expression of some CYPs and above all, in different ways in the GF and SPF mice. In the GF mice, the expression of the DMEs (CYP1A) responsible for the formation of active form of the drug are significantly increased in the small intestine and liver after nabumetone application. These results highlight the importance of gut microbiome in processes involved in drug metabolism in the both gastrointestinal tract and in the liver with possible clinical relevance.

scholarly journals Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

2019 ◽  
Vol 7 (10) ◽  
pp. 456 ◽  
Author(s):  
Kaliyan Barathikannan ◽  
Ramachandran Chelliah ◽  
Momna Rubab ◽  
Eric Banan-Mwine Daliri ◽  
Fazle Elahi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acids ◽  
Genetic Profile ◽  
Fecal Transplantation ◽  
Intestinal Microbes ◽  
Prevalence Of Obesity ◽  
Future Direction ◽  
The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

scholarly journals Microbe-Metabolite Associations Linked to the Rebounding Murine Gut Microbiome Postcolonization with Vancomycin-Resistant Enterococcus faecium

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Andre Mu ◽  
Glen P. Carter ◽  
Lucy Li ◽  
Nicole S. Isles ◽  
Alison F. Vrbanac ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Enterococcus Faecium ◽  
Molecular Mechanisms ◽  
Microbial Community Composition ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Content Type ◽  
Functional Roles ◽  
Specific Pathogen ◽  
Vancomycin Resistant

ABSTRACT Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging antibiotic-resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenericutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone and to subsequent VREfm challenge. Using neural networking approaches to find cooccurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition toward a preantibiotic naive microbiome. This study shows the impacts of antibiotics on the gut ecosystem and the progression of the microbiome in response to colonization with VREfm. Our results offer insights toward identifying potential nonantibiotic alternatives to eliminate VREfm through metabolic reengineering to preferentially select for Bacteroides. IMPORTANCE This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.

scholarly journals Impairment of Intestinal Barrier Function Induced by Early Weaning via Autophagy and Apoptosis Associated With Gut Microbiome and Metabolites

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjie Tang ◽  
Jingliang Liu ◽  
Yanfei Ma ◽  
Yusen Wei ◽  
Jianxin Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Clustering Coefficient ◽  
Autophagic Flux ◽  
Early Weaning ◽  
Microbial Composition ◽  
Apoptosis Pathway

Early weaning piglet is frequently accompanied by severe enteric inflammatory responses and microbiota dysbiosis. The links between the gut microbiome and the etiology of gut inflammation are not fully understood. The study is aimed to investigate the potential molecular mechanisms mediating inflammatory reactivity following early weaning, and to find whether these changes are correlated with gut microbiota and metabolite signatures by comparison between suckling piglets (SPs) and weaning piglets (WPs). Histopathology analysis showed a severe inflammatory response and the disruption of epithelial barrier function. Early weaning resulted in reduced autophagy indicated as the suppression of autophagic flux, whereas induced the TLR4/P38MAPK/IL-1β-mediated apoptotic pathway, as well as activation of the IL-1β precursor. The alpha-diversity and microbial composition were changed in WPs, such as the decreased abundances of Bifidobacterium, Bacteroides, Bacillus, Lactobacillus, and Ruminococcus. Microbial co-concurrence analysis revealed that early weaning significantly decreased network complexity, including network size, degree, average clustering coefficient and number of keystone species, as compared with the SP group. Differentially abundant metabolites were mainly associated with amino acid and purine metabolism. Strong correlations were detected between discrepant microbial taxa and multiple inflammatory parameters. In conclusion, we found that dysregulations of autophagy and apoptosis pathway were involved in colon inflammation during weaned period, which may result from gut microbiota dysbiosis. This study may provide possible intervention modalities for preventing or treating post-weaning infections through maintaining gut microbial ecosystem integrity.

The gut microbiota in pigs: ecology and biotherapeutics

2022 ◽  
pp. 129-164
Author(s):  
Thomas C. A. Hitch ◽  
◽  
David Wylensek ◽  
Jürgen Harlizius ◽  
Thomas Clavel ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Functional Diversity ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Microbial Ecosystem ◽  
Bacterial Consortia

The community of microorganisms inhabiting the intestine of mammals are referred to as the gut microbiome and are known to influence the health of their host. Despite extensive work in the last decades, we still know remarkably little about their diversity and the molecular mechanisms underlying interactions with the host. After reviewing the main methods used to analyse gut microbiomes, we summarize data on the structural and functional diversity of the microbial ecosystem in pigs and also highlight the potential of cultivation and applications based on the use of minimal bacterial consortia.

scholarly journals Microbe-metabolite associations linked to the rebounding murine gut microbiome post-colonization with vancomycin resistant Enterococcus faecium

2019 ◽  
Author(s):  
Andre Mu ◽  
Glen P. Carter ◽  
Lucy Li ◽  
Nicole S. Isles ◽  
Alison F. Vrbanac ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Enterococcus Faecium ◽  
Molecular Mechanisms ◽  
Microbial Community Composition ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Functional Roles ◽  
Specific Pathogen ◽  
Vancomycin Resistant ◽  
Rrna Gene Sequencing

AbstractVancomycin resistant Enterococcus faecium (VREfm) is an emerging antibiotic resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenerricutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone, and to subsequent VREfm challenge. Using neural networking approaches to find co-occurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition towards a pre-antibiotic naïve microbiome. This study shows the impacts of antibiotics on the gut ecosystem, and the progression of the microbiome in response to colonisation with VREfm. Our results offer insights towards identifying potential non-antibiotic alternatives to eliminate VREfm through metabolic re-engineering to preferentially select for Bacteroides.ImportanceThis study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.

scholarly journals Minimizing confounders and increasing data quality in murine models for studies of the gut microbiome

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5166 ◽  
Author(s):  
Jun Miyoshi ◽  
Vanessa Leone ◽  
Kentaro Nobutani ◽  
Mark W. Musch ◽  
Kristina Martinez-Guryn ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Standard Operating Procedure ◽  
Individual Variability ◽  
Rrna Gene ◽  
Murine Models ◽  
Single Room ◽  
Specific Pathogen ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Murine models are widely used to explore host-microbe interactions because of the challenges and limitations inherent to human studies. However, microbiome studies in murine models are not without their nuances. Inter-individual variations in gut microbiota are frequent even in animals housed within the same room. We therefore sought to find an efficient and effective standard operating procedure (SOP) to minimize these effects to improve consistency and reproducibility in murine microbiota studies. Mice were housed in a single room under specific-pathogen free conditions. Soiled cage bedding was routinely mixed weekly and distributed among all cages from weaning (three weeks old) until the onset of the study. Females and males were separated by sex and group-housed (up to five mice/cage) at weaning. 16S rRNA gene analyses of fecal samples showed that this protocol significantly reduced pre-study variability of gut microbiota amongst animals compared to other conventional measures used to normalize microbiota when large experimental cohorts have been required. A significant and consistent effect size was observed in gut microbiota when mice were switched from regular chow to purified diet in both sexes. However, sex and aging appeared to be independent drivers of gut microbial assemblage and should be taken into account in studies of this nature. In summary, we report a practical and effective pre-study SOP for normalizing the gut microbiome of murine cohorts that minimizes inter-individual variability and resolves co-housing problems inherent to male mice. This SOP may increase quality, rigor, and reproducibility of data acquisition and analysis.

More than just a gut instinct–the potential interplay between a baby's nutrition, its gut microbiome, and the epigenome

2013 ◽  
Vol 304 (12) ◽  
pp. R1065-R1069 ◽  
Author(s):  
Mona Mischke ◽  
Torsten Plösch
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acids ◽  
The Body ◽  
Transcriptional Networks ◽  
Adult Obesity ◽  
Active Metabolites ◽  
Early Nutrition ◽  
Major Target

Substantial evidence links early postnatal nutrition to the development of obesity later in life. However, the molecular mechanisms of this connection must be further elucidated. Epigenetic mechanisms have been indicated to be involved in this process, referred to as metabolic programming. Therefore, we propose here that early postnatal nutrition (breast and formula feeding) epigenetically programs the developing organs via modulation of the gut microbiome and influences the body weight phenotype including the predisposition to obesity. Specifically, the early-age food patterns are known to determine the gross composition of the early gut microbiota. In turn, the microbiota produces large quantities of epigenetically active metabolites, such as folate and short chain fatty acids (butyrate and acetate). The spectrum of these produced metabolites depends on the composition of the gut microbiota. Hence, it is likely that changes in gut microbiota that result in altered metabolite composition might influence the epigenome of directly adjacent intestinal cells, as well as other major target cell populations, such as hepatocytes and adipocytes. Nuclear receptors and other transcription factors (the PPARs, LXR, RXR, and others) could be physiologically relevant targets of this metabolite-induced epigenetic regulation. Ultimately, transcriptional networks regulating energy balance could be manipulated. For these reasons, we postulate that early nutrition may influence the baby epigenome via microbial metabolites, which contributes to the observed relationship between early nutrition and adult obesity.

scholarly journals A Review of the Role of Gut microbiome in Obesity

2020 ◽  
Vol 218 ◽  
pp. 03010
Author(s):  
Muxin Zhang
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Excessive Weight Gain ◽  
Global Epidemic ◽  
Intestinal Microbial Community ◽  
Excessive Weight ◽  
Obese Subjects ◽  
Host Metabolism

Obesity has become a global epidemic during the last several years. In addition to genes, lifestyle, socioeconomic status, and other factors that mainly give rise to obesity, gut microbiome recently has aroused great concern for its pivotal role in obesity and host metabolism. A great number of studies have done to uncover the inner associations between gut microbiota and obesity. Among the commonly reported findings, the phylum of Firmicutes and Bacteroidetes are highly related to excessive weight gain, with a higher ratio of F/B in obese subjects. In this review, we summarized some important studies focusing on the alteration and possible role of different bacterial taxa affecting obesity. We also discussed the diet effect on intestinal microbial community and potential molecular mechanisms of energy metabolism involved by gut microbiota.

scholarly journals Emerging Roles for the Gut Microbiome in Lymphoid Neoplasms

2021 ◽  
Vol 15 ◽  
pp. 117955492110241
Author(s):  
Zhuangzhuang Shi ◽  
Mingzhi Zhang
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Disease Burden ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Physiological Processes ◽  
Lymphoid Neoplasms ◽  
Promising Target ◽  
Preclinical And Clinical Studies

Lymphoid neoplasms encompass a heterogeneous group of malignancies with a predilection for immunocompromised individuals, and the disease burden of lymphoid neoplasms has been rising globally over the last decade. At the same time, mounting studies delineated a crucial role of the gut microbiome in the aetiopathogenesis of various diseases. Orchestrated interactions between myriad microorganisms and the gastrointestinal mucosa establish a defensive barrier for a range of physiological processes, especially immunity and metabolism. These findings provide new perspectives to harness our knowledge of the gut microbiota for preclinical and clinical studies of lymphoma. Here, we review recent findings that support a role for the gut microbiota in the development of lymphoid neoplasms and pinpoint relevant molecular mechanisms. Accordingly, we propose the microbiota-gut-lymphoma axis as a promising target for clinical translation, including auxiliary diagnosis, novel prevention and treatment strategies, and predicting clinical outcomes and treatment-related adverse effects of the disease in the future. This review will reveal a fascinating avenue of research in the microbiota-mediated lymphoma field.

Sign in / Sign up

Export Citation Format

Share Document