Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota

AbstractThe human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs) that are ancient components of immune defence. Despite important medical relevance, it has remained unclear whether AMP resistance genes in the gut microbiome are available for genetic exchange between bacterial species. Here we show that AMP- and antibiotic-resistance genes differ in their mobilization patterns and functional compatibilities with new bacterial hosts. First, whereas AMP resistance genes are widespread in the gut microbiome, their rate of horizontal transfer is lower than that of antibiotic resistance genes. Second, gut microbiota culturing and functional metagenomics revealed that AMP resistance genes originating from phylogenetically distant bacteria only have a limited potential to confer resistance inEscherichia coli, an intrinsically susceptible species. Third, the phenotypic impact of acquired AMP resistance genes heavily depends on the genetic background of the recipient bacteria. Taken together, functional compatibility with the new bacterial host emerges as a key factor limiting the genetic exchange of AMP resistance genes. Finally, our results suggest that AMPs induce highly specific changes in the composition of the human microbiota with implications for disease risks.

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Metagenomics-Based Analysis of the Age-Related Cumulative Effect of Antibiotic Resistance Genes in Gut Microbiota

Antibiotics ◽

10.3390/antibiotics10081006 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1006

Author(s):

Lei Wu ◽

Xinqiang Xie ◽

Ying Li ◽

Tingting Liang ◽

Haojie Zhong ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Tetracycline Resistance ◽

Cumulative Effect ◽

Resistance Mechanisms ◽

Human Gut ◽

Human Gut Microbiota ◽

Age Related

Antibiotic resistance in bacteria has become a major global health problem. One of the main reservoirs of antibiotic resistance genes is the human gut microbiota. To characterise these genes, a metagenomic approach was used. In this study, a comprehensive antibiotic resistome catalog was established using fecal samples from 246 healthy individuals from world’s longevity township in Jiaoling, China. In total, 606 antibiotic resistance genes were detected. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate and become more complex with age as older groups harbour the highest abundance of these genes. Tetracycline resistance gene type tetQ was the most abundant group of antibiotic resistance genes in gut microbiota, and the main carrier of antibiotic resistance genes was Bacteroides. Antibiotic efflux, inactivation, and target alteration were found to be the dominant antimicrobial resistance mechanisms. This research may help to establish a comprehensive antibiotic resistance catalog that includes extremely long-lived healthy people such as centenarians, and may provide potential recommendations for controlling the use of antibiotics.

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The human gut resistome

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2014.0087 ◽

2015 ◽

Vol 370 (1670) ◽

pp. 20140087 ◽

Cited By ~ 146

Author(s):

Willem van Schaik

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Resistance Genes ◽

Horizontal Transfer ◽

Genetic Material ◽

Antibiotic Resistance Genes ◽

Strictly Anaerobic ◽

Donor Strain ◽

Human Gut ◽

Frequent Event

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota (‘the gut resistome’). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium .

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Prevalence of Antibiotic Resistance Genes among Human Gut-Derived Bifidobacteria

Applied and Environmental Microbiology ◽

10.1128/aem.02894-16 ◽

2016 ◽

Vol 83 (3) ◽

Cited By ~ 37

Author(s):

Sabrina Duranti ◽

Gabriele Andrea Lugli ◽

Leonardo Mancabelli ◽

Francesca Turroni ◽

Christian Milani ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Resistance Genes ◽

Bacterial Communities ◽

Life Stage ◽

Antibiotic Resistance Genes ◽

Later Life ◽

Limited Information ◽

Human Gut ◽

Content Type

ABSTRACT The microbiota of the human gastrointestinal tract (GIT) may regularly be exposed to antibiotics, which are used to prevent and treat infectious diseases caused by bacteria and fungi. Bacterial communities of the gut retain a reservoir of antibiotic resistance (AR) genes, and antibiotic therapy thus positively selects for those microorganisms that harbor such genetic features, causing microbiota modulation. During the first months following birth, bifidobacteria represent some of the most dominant components of the human gut microbiota, although little is known about their AR gene complement (or resistome). In the current study, we assessed the resistome of the Bifidobacterium genus based on phenotypic and genotypic data of members that represent all currently recognized bifidobacterial (sub)species. Moreover, a comparison between the bifidobacterial resistome and gut metagenome data sets from adults and infants shows that the bifidobacterial community present at the first week following birth possesses a reduced AR arsenal compared to that present in the infant bifidobacterial population in subsequent weeks of the first year of life. Our findings reinforce the concept that the early infant gut microbiota is more susceptible to disturbances by antibiotic treatment than the gut microbiota developed at a later life stage. IMPORTANCE The spread of resistance to antibiotics among bacterial communities has represented a major concern since their discovery in the last century. The risk of genetic transfer of resistance genes between microorganisms has been extensively investigated due to its relevance to human health. In contrast, there is only limited information available on antibiotic resistance among human gut commensal microorganisms such as bifidobacteria, which are widely exploited by the food industry as health-promoting microorganisms or probiotic ingredients. In the current study, we explored the occurrence of antibiotic resistance genes in the genomes of bifidobacteria and evaluated their genetic mobility to other human gut commensal microorganisms.

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Horizontal transfer of antibiotic resistance genes in the human gut microbiome

Current Opinion in Microbiology ◽

10.1016/j.mib.2020.02.002 ◽

2020 ◽

Vol 53 ◽

pp. 35-43 ◽

Cited By ~ 13

Author(s):

Ross S McInnes ◽

Gregory E McCallum ◽

Lisa E Lamberte ◽

Willem van Schaik

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Gut Microbiome ◽

Horizontal Transfer ◽

Antibiotic Resistance Genes ◽

Human Gut ◽

Human Gut Microbiome

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Metagenomic profiles and antibiotic resistance genes in gut microbiota of mice exposed to arsenic and iron

Chemosphere ◽

10.1016/j.chemosphere.2014.03.068 ◽

2014 ◽

Vol 112 ◽

pp. 1-8 ◽

Cited By ~ 42

Author(s):

Xuechao Guo ◽

Su Liu ◽

Zhu Wang ◽

Xu-xiang Zhang ◽

Mei Li ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Resistance Genes ◽

Antibiotic Resistance Genes

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Dynamic changes in Antibiotic Resistance Genes and Gut Microbiota after H. Pylori Eradication Therapies

10.21203/rs.3.rs-777700/v1 ◽

2021 ◽

Author(s):

LINGLING WANG ◽

Haobin Yao ◽

Tereasa Tong ◽

KS Lau ◽

Suet Yi Leung ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gut Microbiota ◽

Resistance Genes ◽

Eradication Therapy ◽

Antibiotic Resistance Genes ◽

Short Term ◽

Significant Difference ◽

Treatment Naïve ◽

Stool Samples ◽

H Pylori

Abstract Background: Short-term antibiotics exposure is associated with alterations in microbiota and antibiotic resistance genes (ARGs) in the human gut. While antibiotics are critical in the successful eradication of Helicobacter pylori, the short-term and long-term impacts on the composition and quantity of antibiotics resistance genes after H. pylori eradication is unclear. This study used whole genome shotgun metagenomic of stool samples to characterize the gut microbiota and ARGs, before and after H. pylori eradication therapy. Results: Forty-four H. pylori-infected patients were recruited including 21 treatment naïve patients who received clarithromycin-based triple therapy (CLA group) and 23 patients who failed previous therapies, in which 10 received levofloxacin-based quadruple therapy [LEVO group] and 13 received other combinations [OTHER group] in the current study. Stool samples were collected at baseline (before current treatment), 6-week and 6-month after eradication therapy. At baseline, there was only a slight difference among the three groups on ARGs and gut microbiota. After eradication therapy, there was a transient but significant increase in gut ARGs 6-week post-therapy, among which the LEVO group had the most significant ARGs alteration compared to other two groups. For treatment naïve patients, those with higher ARG richness and ErmF abundance were prone to fail CLA eradication. For gut microbiota, the bacteria richness decreased at 6-week and there was a significant difference in microbiota community among the three groups at 6-week. Conclusions: Our findings demonstrated the dynamic alterations in gut microbiota and ARGs induced by different eradication therapies, which could influence the choices of antibiotics in eradication therapy.

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