Dysbiosis individualizes the fitness effect of antibiotic resistance in the mammalian gut

Cardoso, Luís Leónidas; Durão, Paulo; Amicone, Massimo; Gordo, Isabel

doi:10.1038/s41559-020-1235-1

Cited by 24 publications

(21 citation statements)

References 83 publications

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“…Therefore, an important mechanism underlying individualized responses to antibiotics is the individualized microbiota at baseline. Considering that only a small fraction of gut microbiota is shared among healthy individuals [ 38 , 39 ], our results explain the previous observations that the microbiota in different individuals responds differently to antibiotics [ 2 , 40 ]. This is also consistent with the role of pre-treatment microbiota in determining response to fecal microbiota transplantation (FMT) [ 41 ] and dietary interventions [ 42 ].…”

Section: Discussionsupporting

confidence: 85%

Gut microbiota response to antibiotics is personalized and depends on baseline microbiota

et al. 2021

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Background The magnitude of microbiota perturbations after exposure to antibiotics varies among individuals. It has been suggested that the composition of pre-treatment microbiota underpins personalized responses to antibiotics. However, this hypothesis has not been directly tested in humans. In this high-throughput amplicon study, we analyzed 16S ribosomal RNA gene sequences of 260 stool samples collected twice weekly from 39 patients with acute leukemia during their ~ 4 weeks of hospitalization for chemotherapy while they received multiple antibiotics. Results Despite heavy and sustained antibiotic pressure, microbial communities in samples from the same patient remained more similar to one another than to those from other patients. Principal component mixed effect regression using microbiota and granular antibiotic exposure data showed that microbiota departures from baseline depend on the composition of the pre-treatment microbiota. Penalized generalized estimating equations identified 6 taxa within pre-treatment microbiota that predicted the extent of antibiotic-induced perturbations. Conclusions Our results indicate that specific species in pre-treatment microbiota determine personalized microbiota responses to antibiotics in humans. Thus, precision interventions targeting pre-treatment microbiota may prevent antibiotic-induced dysbiosis and its adverse clinical consequences.

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Section: Discussionsupporting

confidence: 85%

Gut microbiota response to antibiotics is personalized and depends on baseline microbiota

et al. 2021

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“…In addition, the observation that persistent resistome disruption is observed (in stool) more than three months after supplementation ceases, suggest that the effects of probiotics on the gut resistome may be persistent and thus increase the chance of horizontal gene transfer events. The persistent post-antibiotics dysbiosis associated with probiotics 27 may also contribute to ARG persistence since it can reduce the fitness cost of carrying ARGs 42 . Notably, in this work, probiotics were supplemented after antibiotics and not concomitantly to disentangle the effects of probiotics and antibiotics on the gut microbiome.…”

Section: Discussionmentioning

confidence: 99%

Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner

et al. 2021

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Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.

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“…Besides the presence of lactose, differences between measurements likely reflect the common variation in microbiota composition between individuals which is known to further increase with the antibiotic treatment ( Leónidas Cardoso et al, 2020 ). The effect of the chosen antibiotic regime was assessed by estimating the Bray-Curtis beta diversity, a measure of group heterogeneity, before and after antibiotic treatment in an independent set of 5 animals.…”

Section: Resultsmentioning

confidence: 99%

The Selective Advantage of the lac Operon for Escherichia coli Is Conditional on Diet and Microbiota Composition

et al. 2021

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The lac operon is one of the best known gene regulatory circuits and constitutes a landmark example of how bacteria tune their metabolism to nutritional conditions. It is nearly ubiquitous in Escherichia coli strains justifying the use of its phenotype, the ability to consume lactose, for species identification. Lactose is the primary sugar found in milk, which is abundant in mammals during the first weeks of life. However, lactose is virtually non-existent after the weaning period, with humans being an exception as many consume dairy products throughout their lives. The absence of lactose during adulthood in most mammals and the rarity of lactose in the environment, means that the selective pressure for maintaining the lac operon could be weak for long periods of time. Despite the ability to metabolize lactose being a hallmark of E. coli’s success when colonizing its primary habitat, the mammalian intestine, the selective value of this trait remains unknown in this ecosystem during adulthood. Here we determine the competitive advantage conferred by the lac operon to a commensal strain of E. coli when colonizing the mouse gut. We find that its benefit, which can be as high as 11%, is contingent on the presence of lactose in the diet and on the presence of other microbiota members in the gut, but the operon is never deleterious. These results help explaining the pervasiveness of the lac operon in E. coli, but also its polymorphism, as lac-negative E. coli strains albeit rare can naturally occur in the gut.

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Dysbiosis individualizes the fitness effect of antibiotic resistance in the mammalian gut

Cited by 24 publications

References 83 publications

Gut microbiota response to antibiotics is personalized and depends on baseline microbiota

Gut microbiota response to antibiotics is personalized and depends on baseline microbiota

Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner

The Selective Advantage of the lac Operon for Escherichia coli Is Conditional on Diet and Microbiota Composition

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