scholarly journals Antibiotic-induced depletion of gut microbiota increases systemic exposure of clopidogrel active metabolite in type 2 diabetic rats

2021 ◽  
Author(s):  
Xue Chen ◽  
Yingrui Liu ◽  
Hongwei Yao ◽  
Wenfang Song ◽  
Meng Pan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
Active Metabolite ◽  
Systemic Exposure ◽  
Antibiotic Administration ◽  
Microbial Composition ◽  
16S Rrna Sequence ◽  
Direct Role ◽  
Fecal Microbiome ◽  
Antibiotic Cocktail

Background and Purpose: The current study investigated whether the manipulation of gut microbiome through treatment with an antibiotic cocktail can alter the bioavailability of clopidogrel active metabolite (Clop-AM) in T2DM rats. Experimental Approach: Control and T2DM rats were orally administered with either vehicle or an antibiotic cocktail containing ampicillin, neomycin, metronidazole, and vancomycin for 5 consecutive days. The levels of clopidogrel (Clop) and its metabolites were measured by LC-MS/MS. Biochemical parameters, liver microsome metabolism, mRNA, protein or activity of Clop- metabolizing enzymes and transporter, and 16S rRNA sequence of fecal samples were analyzed to explain any altered pharmacokinetic profile of Clop-AM. Key Results: Antibiotic administration markedly alleviated T2DM rats’ phenotypes including hyperglycemia, hyperlipidemia, insulin resistance, liver dysfunction and inflammation. Meanwhile, the reduced systemic exposure of Clop-AM in T2DM rats as compared to control rats was significantly reversed after antibiotic treatment, accompanied with the decreased expression of P-glycoprotein (P-gp) in small intestine, suggesting P-gp-based Clop absorption might be promoted, consequently making more Clop available for Clop-AM formation. Interestingly, fecal microbiome analysis exhibited the reduced microbial amount and the altered microbial composition in antibiotic-treated T2DM rats. Especially, there was an inconsistent change of P-gp levels between T2DM rats and SW480 cells after antibiotic treatment, suggesting antibiotic-induced microbiome depletion, not the direct role of antibiotics is associated with the enhanced Clop-AM plasma exposure in T2DM rats. Conclusion and Implication: The findings show that gut microbiota modulation is an effective therapeutic strategy to enhance Clop-AM generation under T2DM conditions.

scholarly journals Emergence of nosocomial associated opportunistic pathogens in the gut microbiome after antibiotic treatment

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Isaac Raplee ◽  
Lacey Walker ◽  
Lei Xu ◽  
Anil Surathu ◽  
Ashok Chockalingam ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antibiotic Therapy ◽  
Antibiotic Treatment ◽  
Nosocomial Infections ◽  
Pathogenic Bacteria ◽  
Antibiotic Administration ◽  
Oral Antibiotic ◽  
Opportunistic Pathogens ◽  
Taxonomic Assignment ◽  
Antibiotic Resistant

Abstract Introduction According to the Centers for Disease Control’s 2015 Hospital Acquired Infection Hospital Prevalence Survey, 1 in 31 hospital patients was infected with at least one nosocomial pathogen while being treated for unrelated issues. Many studies associate antibiotic administration with nosocomial infection occurrence. However, to our knowledge, there is little to no direct evidence of antibiotic administration selecting for nosocomial opportunistic pathogens. Aim This study aims to confirm gut microbiota shifts in an animal model of antibiotic treatment to determine whether antibiotic use favors pathogenic bacteria. Methodology We utilized next-generation sequencing and in-house metagenomic assembly and taxonomic assignment pipelines on the fecal microbiota of a urinary tract infection mouse model with and without antibiotic treatment. Results Antibiotic therapy decreased the number of detectable species of bacteria by at least 20-fold. Furthermore, the gut microbiota of antibiotic treated mice had a significant increase of opportunistic pathogens that have been implicated in nosocomial infections, like Acinetobacter calcoaceticus/baumannii complex, Chlamydia abortus, Bacteroides fragilis, and Bacteroides thetaiotaomicron. Moreover, antibiotic treatment selected for antibiotic resistant gene enriched subpopulations for many of these opportunistic pathogens. Conclusions Oral antibiotic therapy may select for common opportunistic pathogens responsible for nosocomial infections. In this study opportunistic pathogens present after antibiotic therapy harbored more antibiotic resistant genes than populations of opportunistic pathogens before treatment. Our results demonstrate the effects of antibiotic therapy on induced dysbiosis and expansion of opportunistic pathogen populations and antibiotic resistant subpopulations of those pathogens. Follow-up studies with larger samples sizes and potentially controlled clinical investigations should be performed to confirm our findings.

scholarly journals Antibiotic Treatment Drives the Diversification of the Human Gut Resistome

2019 ◽  
Author(s):  
Jun Li ◽  
Elizabeth A. Rettedal ◽  
Eric van der Helm ◽  
Mostafa Ellabaan ◽  
Gianni Panagiotou ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
Resistance Genes ◽  
Community Dynamics ◽  
Antibiotic Resistance Genes ◽  
Strain Level ◽  
Functional Study ◽  
Antibiotic Administration ◽  
Bacterial Community Dynamics ◽  
The Impact

AbstractDespite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that short-term antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ∼3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.

scholarly journals Community composition and development of the post-weaning piglet gut microbiome

2020 ◽  
Author(s):  
Daniela Gaio ◽  
Matthew Z DeMaere ◽  
Kay Anantanawat ◽  
Graeme J Eamens ◽  
Michael Liu ◽  
...  
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
Community Composition ◽  
Antibiotic Treatment ◽  
Gut Microbiome ◽  
Treatment Effects ◽  
Sequence Data ◽  
Microbial Community Composition ◽  
Dominant Factor ◽  
Microbial Composition

Abstract BackgroundEarly weaning and intensive farming practices predispose piglets to the development of infectious and often lethal diseases, against which antibiotics are used. Besides contributing to the build-up of antimicrobial resistance, antibiotics are known to modulate the gut microbial composition. Studies have previously investigated the effects of probiotics as alternatives to antibiotic treatment for the prevention of post-weaning diarrhea. In order to describe the post-weaning gut microbiota, and the effects of two probiotics formulations and of intramuscular antibiotic treatment on the gut microbiota, we processed over 800 faecal time-series samples from 126 piglets and 42 sows, generating over 8Tbp of metagenomic shotgun sequence data. Here we describe the animal trial procedures, the generation of our metagenomic dataset and the analysis of the microbial community composition using a phylogenetic framework.ResultsFactors such as age, litter effects, and breed, by significantly correlating with gut microbial community shifts, can be major confounding factors in the assessment of treatment effects. Intramuscular antibiotic treatment and probiotic treatments were found to correlate with alpha and beta diversity, as well as with a transient establishment of Mollicutes and Lactobacillales, respectively. We found the abundance of certain taxa to correlate with weight gain.ConclusionsOur findings demonstrate that breed, litter, and age, are important contributors to variation in the community composition, and that treatment effects of the antibiotic and probiotic treatments were subtle, while host age was the dominant factor in shaping the gut microbiota of piglets after weaning. The current study shows, by means of a phylogenetic diversity framework, that the post-weaning pig gut microbiome appears to follow a highly structured developmental program with characteristic post-weaning changes that can distinguish hosts that were born as little as two days apart in the second month of life.

scholarly journals Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gilliard Lach ◽  
Christine Fülling ◽  
Thomaz F. S. Bastiaanssen ◽  
Fiona Fouhy ◽  
Aoife N. O’ Donovan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
Brain Function ◽  
Early Life ◽  
Microbiota Composition ◽  
Microbial Composition ◽  
Extrinsic Factors ◽  
Neurobehavioral Effects ◽  
Adolescent Period

Abstract The gut microbiota is an essential regulator of many aspects of host physiology. Disruption of gut microbial communities affects gut-brain communication which ultimately can manifest as changes in brain function and behaviour. Transient changes in gut microbial composition can be induced by various intrinsic and extrinsic factors, however, it is possible that enduring shifts in the microbiota composition can be achieved by perturbation at a timepoint when the gut microbiota has not fully matured or is generally unstable, such as during early life or ageing. In this study, we investigated the effects of 3-week microbiota depletion with antibiotic treatment during the adolescent period and in adulthood. Following a washout period to restore the gut microbiota, behavioural and molecular hallmarks of gut-brain communication were investigated. Our data revealed that transient microbiota depletion had long-lasting effects on microbiota composition and increased anxiety-like behaviour in mice exposed to antibiotic treatment during adolescence but not in adulthood. Similarly, gene expression in the amygdala was more severely affected in mice treated during adolescence. Taken together these data highlight the vulnerability of the gut microbiota during the critical adolescent period and the long-lasting impact manipulations of the microbiota can have on gene expression and behaviour in adulthood.

scholarly journals Minireview: Gut Microbiota: The Neglected Endocrine Organ

2014 ◽  
Vol 28 (8) ◽  
pp. 1221-1238 ◽  
Author(s):  
Gerard Clarke ◽  
Roman M. Stilling ◽  
Paul J. Kennedy ◽  
Catherine Stanton ◽  
John F. Cryan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
Body Weight Gain ◽  
Bacterial Species ◽  
Plasma Concentrations ◽  
Regulatory Control ◽  
Microbial Composition ◽  
Direct Role ◽  
Endocrine Organ

The concept that the gut microbiota serves as a virtual endocrine organ arises from a number of important observations. Evidence for a direct role arises from its metabolic capacity to produce and regulate multiple compounds that reach the circulation and act to influence the function of distal organs and systems. For example, metabolism of carbohydrates results in the production of short-chain fatty acids, such as butyrate and propionate, which provide an important source of nutrients as well as regulatory control of the host digestive system. This influence over host metabolism is also seen in the ability of the prebiotic inulin to influence production of relevant hormones such as glucagon-like peptide-1, peptide YY, ghrelin, and leptin. Moreover, the probiotic Lactobacillus rhamnosus PL60, which produces conjugated linoleic acid, has been shown to reduce body-weight gain and white adipose tissue without effects on food intake. Manipulating the microbial composition of the gastrointestinal tract modulates plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Indirectly and through as yet unknown mechanisms, the gut microbiota exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from studies on animals raised in a germ-free environment, who show exaggerated responses to psychological stress, which normalizes after monocolonization by certain bacterial species including Bifidobacterium infantis. It is tempting to speculate that therapeutic targeting of the gut microbiota may be useful in treating stress-related disorders and metabolic diseases.

scholarly journals Expansion and persistence of antibiotic-specific resistance genes following antibiotic treatment

2020 ◽  
Author(s):  
Kang Kang ◽  
Lejla Imamovic ◽  
Maria-Anna Misiakou ◽  
Maria Bornakke Sørensen ◽  
Yoshitaro Heshiki ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gut Microbiota ◽  
Resistance Gene ◽  
Antibiotic Treatment ◽  
Relative Abundance ◽  
Resistance Genes ◽  
Specific Resistance ◽  
Specific Gene ◽  
Antibiotic Administration ◽  
Human Gut

Abstract Background. Oral antibiotics are commonly prescribed to non-hospitalized adults. However, antibiotic-induced changes on the human gut microbiome are often investigated in cohorts with pre-existing health conditions and/or concomitant medication, leaving the effects of antibiotics not completely understood.Results. We used a combination of omic approaches to comprehensively assess the effects of antibiotics on the gut microbiota and particularly the gut resistome of a small cohort of healthy adults. We observed that 3 to 19 species per individual proliferated during antibiotic treatment and Gram-negative species expanded significantly in relative abundance. While the overall relative abundance of antibiotic resistance gene homologues did not significantly change, antibiotic-specific gene homologues with presumed resistance towards the administered antibiotics were common in proliferating species and significantly increased in relative abundance. Virome sequencing and plasmid analysis showed the expansion of antibiotic-specific resistance gene homologues even three months after antibiotic administration, while paired-end read analysis suggested their dissemination among different species.Conclusions. These results suggest that antibiotic treatment can lead to a persistent expansion of antibiotic resistance genes in the human gut microbiota and provide further data in support of good antibiotic stewardship.

scholarly journals Effects of treatment with three antibiotics, vancomycin, neomycin, and AVNM on gut microbiome in C57BL/6 mice

2021 ◽  
Author(s):  
Pratikshya Ray ◽  
Subhayan Chakraborty ◽  
Arindam Ghosh ◽  
Palok Aich
Keyword(s):  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Microbial Composition ◽  
Immune Genes ◽  
Antibiotic Cocktail ◽  
Tnf Α ◽  
Bacteroidetes Phylum ◽  
Physiological Homeostasis ◽  
Ifn Γ ◽  
Vancomycin Treatment

AbstractHigher organisms, especially mammals, harbor diverse microbiota in the gut that plays a major role in maintaining health and physiological homeostasis. Perturbation of gut flora helps identifying their roles. Antibiotics are potent perturbing agents of microbiome. Select antibiotics like vancomycin, neomycin, and AVNM (an antibiotic cocktail containing ampicillin, vancomycin, neomycin, and metronidazole) were used to perturb the gut microbiota of C57BL/6 male mice to understand their roles in host immunity and metabolism. The current study revealed that the resulting gut microbial composition was different, and diversity (at the phylum and genus level) was reduced differentially following each antibiotic treatment. Vancomycin treatment caused a significant increase in Verrucomicrobia and Proteobacteria phyla. The treatment with neomycin yielded an increase in the Bacteroidetes phylum, while the treatment with AVNM led to an increase in Proteobacteria phylum with lowest diversity of microbiome in the gut. The current results also revealed that the different antibiotics treatment caused variation in the cecal index, expression of immune genes (TNF-α, IL-10, IFN-γ) in the colon, and short-chain fatty acids (SCFA) level in the blood of mice. A strong correlation was observed for antibiotic-induced differential dysbiosis patterns of gut microbiota and the altered immune and SCFA profile of the host. The outcome of the present study could be clinically important.

scholarly journals Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Li ◽  
Yuting Cai ◽  
Qian Huang ◽  
Wei Tan ◽  
Bingyan Li ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Choroidal Neovascularization ◽  
16S Rrna Gene Sequencing ◽  
Age Related Macular Degeneration ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Fecal Microbiome ◽  
Age Related ◽  
Rrna Gene Sequencing

PurposeChoroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.MethodsThe feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.ResultsThe gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.ConclusionThe study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.

scholarly journals Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant

2018 ◽  
Vol 10 (460) ◽  
pp. eaap9489 ◽  
Author(s):  
Ying Taur ◽  
Katharine Coyte ◽  
Jonas Schluter ◽  
Elizabeth Robilotti ◽  
Cesar Figueroa ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antibiotic Treatment ◽  
Intestinal Microbiota ◽  
Fecal Microbiota ◽  
Commensal Bacteria ◽  
Controlled Clinical Trial ◽  
Antibiotic Administration ◽  
Fecal Microbiota Transplant ◽  
Hematopoietic Stem ◽  
Microbiota Diversity

Antibiotic treatment can deplete the commensal bacteria of a patient’s gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient’s gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.

scholarly journals Effects of Malted Rice Amazake on Constipation Symptoms and Gut Microbiota in Children and Adults with Severe Motor and Intellectual Disabilities: A Pilot Study

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4466
Author(s):  
Suzumi Kageyama ◽  
Rikako Inoue ◽  
Koji Hosomi ◽  
Jonguk Park ◽  
Hitomi Yumioka ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intellectual Disabilities ◽  
Fermented Food ◽  
16S Rrna Sequence ◽  
Fecal Microbiome ◽  
Severe Motor ◽  
Sequence Method ◽  
The Difference ◽  
Group 2 ◽  
Group 1

Constipation is a frequent complication in patients with severe motor and intellectual disabilities (SMID). The aim of this study was to investigate changes in constipation symptoms and gut microbiota associated with the intake of malted rice amazake, a fermented food in Japan, in patients with SMID. Ten patients consumed the test food for six weeks, and their physical condition, dietary and medication status, and constipation assessment scale (CAS) were investigated. Comprehensive fecal microbiome analysis using the 16S rRNA sequence method was performed. The results showed a significant decrease in CAS, and a significant increase in Lactobacillales and decrease in Escherichia-Shigella after consuming malted rice amazake. To investigate the difference in the effects of malted rice amazake consumption, based on the characteristics of the original gut microbiota, the patients were grouped according to the similarity of their gut microbiota before the intervention; Firmicutes-rich Group 1 (n = 5), Actinobacteria-rich Group 2 (n = 4), and Proteobacteria-rich Group 3 (n = 1). The CAS decreased in Groups 1 and 2. The relative abundance of Bifidobacterium showed an increasing tendency both overall and in Group 1, but it was originally higher in Group 2. Our results suggest that malted rice amazake consumption reduces constipation symptoms and simultaneously changes the gut microbiota, but the changes may vary depending on the original composition of the gut microbiota.

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