Recovery of gut microbiota of healthy adults following antibiotic exposure

Pallejà, Albert; Mikkelsen, Kristian Hallundbæk; Forslund, Kristoffer; Kashani, Alireza; Allin, Kristine H.; Nielsen, Trine; Hansen, Tue H.; Liang, Suisha; Feng, Qiang; Zhang, Chenchen; Pyl, Paul Theodor; Coelho, Luís Pedro; Yang, Huanming; Wang, Jian; Typas, Athanasios; Nielsen, Morten Holtegaard; Nielsen, Henrik Bjørn; Bork, Peer; Wang, Jun; Vilsbøll, Tina; Hansen, Torben; Knop, Filip K.; Arumugam, Manimozhiyan; Pedersen, Oluf

doi:10.1038/s41564-018-0257-9

Cited by 518 publications

(446 citation statements)

References 71 publications

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“…For example, ciprofloxacin treatment shifts the microbial composition and causes reduced microbial diversity within 3‐4 days of treatment . Even though most of the antibiotic‐induced changes in the gut microbial composition returned to pretreatment levels within days or weeks after completed treatment, some changes persisted for longer periods or did not even return to pretreatment levels within the 10‐month to 2‐year follow‐up period in these studies …”

Section: Factors Influencing the Microbial Compositionmentioning

confidence: 74%

“…36 Even though most of the antibiotic-induced changes in the gut microbial composition returned to pretreatment levels within days or weeks after completed treatment, some changes persisted for longer periods or did not even return to pretreatment levels within the 10-month to 2-year follow-up period in these studies. 31,[36][37][38] Thus, the gut microbiota composition is dependent on environmental factors, although the genetics of the host also influence the microbial composition. The importance of the host genetics on the microbiota composition has been highlighted in studies using the TwinsUK population.…”

Section: Fac Tor S Influen Cing the Microb Ial Comp Os Itionmentioning

confidence: 99%

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The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

Heiss

Olofsson

2019

J Neuroendocrinology

184

110

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The gut microbiota has emerged as an environmental factor that modulates the development of the central nervous system (CNS) and the enteric nervous system (ENS). Before obtaining its own microbiota, eutherian foetuses are exposed to products and metabolites from the maternal microbiota. At birth, the infants are colonised by microorganisms. The microbial composition in early life is strongly influenced by the mode of delivery, the feeding method, the use of antibiotics and the maternal microbial composition. Microbial products and microbially produced metabolites act as signalling molecules that have direct or indirect effects on the CNS and the ENS. An increasing number of studies show that the gut microbiota can modulate important processes during development, including neurogenesis, myelination, glial cell function, synaptic pruning and blood‐brain barrier permeability. Furthermore, numerous studies indicate that there is a developmental window early in life during which the gut microbial composition is crucial and perturbation of the gut microbiota during this period causes long‐lasting effects on the development of the CNS and the ENS. However, other functions are readily modulated in adult animals, including microglia activation and neuroinflammation. Several neurobehavioural, neurodegenerative, mental and metabolic disorders, including Parkinson disease, autism spectrum disorder, schizophrenia, Alzheimer's disease, depression and obesity, have been linked to the gut microbiota. This review focuses on the role of the microorganisms in the development and function of the CNS and the ENS, as well as their potential role in pathogenesis.

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Section: Factors Influencing the Microbial Compositionmentioning

confidence: 74%

Section: Fac Tor S Influen Cing the Microb Ial Comp Os Itionmentioning

confidence: 99%

The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

Heiss

Olofsson

2019

J Neuroendocrinology

184

110

View full text Add to dashboard Cite

show abstract

“…Pharmacokinetics of orally administered antibiotics suggests that the oral cavity and oesophagus would be only briefly exposed to the antibiotic during swallowing, whilst the gut is exposed over a more prolonged period.As antibiotics transit through the intestinal tract, they are gradually absorbed via the intestinal epithelium into the bloodstream. Therefore, microbes in the gut exposed to antibiotics for a longer period of time due to their increased bioavailability will receive higher antibiotic selection pressures than those in the oral cavity 40 . The incidences where the oral cavity is likely to acquire ARGs from selective pressures of local antibiotics are from topical antibiotics for periodontal infections or orally-administered antibiotics being absorbed into the bloodstream.…”

Section: Comparisons Between Oral and Gut Resistomes Reveal Differencmentioning

confidence: 99%

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

Carr

Witherden

Lee

et al. 2019

Preprint

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The global threat of the "antimicrobial resistance apocalypse" that has arisen in recent years has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the "resistome", in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes, and little is known about their abundance and diversity, or how their profile compares with antimicrobial resistance genes in the gut. Here we analyse the resistome profiles of 788 oral cavities worldwide and compare these profiles with paired stool samples from shotgun metagenomic data. We find country and body site-specific differences in the prevalence of antimicrobial resistance genes, classes and mechanisms in oral and stool samples. However, the 1 1 abundance of these antimicrobial resistance classes do not correlate with antibiotic prescription rates. A greater similarity was found in interpersonal resistomes between the same body sites than intrapersonal resistomes across different body sites. Between individuals, the oral cavity contains the highest and lowest abundances of specific antimicrobial resistance genes, but a lower diversity of resistance genes compared to the gut, which is likely influenced by differences in microbial composition and exposure to antimicrobial selection pressures. Co-occurrence analysis shows contrasting ARG-species associations between saliva and stool samples. This is the first study to date that characterises the oral cavity resistome worldwide, identifying its distinctive signatures compared to the gut.Maintenance and persistence of antimicrobial resistance is likely to vary across different body sites. Thus, we highlight the importance of characterising the resistome across body sites to uncover the antimicrobial resistance potential in the human body.

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“…The magnitude of changes we observed was greater than expected in healthy subjects. Previous studies tracking recovery of the gut microbiome in healthy people after broad-spectrum antibiotics observed perturbation followed by consistent recovery of microbial communities-loss of bacteria followed by regain of the same bacteria ( Figure S1a) (28) .…”

Section: Antibiotics Destabilized the Microbiome Of Ibd Patientsmentioning

confidence: 58%

Dynamic colonization of microbes and their functions after fecal microbiota transplantation for inflammatory bowel disease

Crothers

Nguyen

Kearney

et al. 2019

Preprint

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For fecal microbiota transplantation (FMT) to be successful in complex immune diseases like inflammatory bowel disease (IBD), it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize the recipient and persist in sufficient quantity and for a long enough period of time to result in a clinical benefit. But few studies have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial and immune functions. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered a range of competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening clinical symptoms. We similarly evaluated transfer of microbial functions, including desired ones like butyrate production and unintended ones like antibiotic resistance. By profiling bacteria coated with IgA, we identified IgA-coated bacteria associated with inflammation, and we found that microbial interactions with the host immune system can be transferred across people. This transfer of immune function is likely critical for gut microbiome therapeutics for immune-related diseases. Our findings elucidate the colonization dynamics of gut microbes as well as their functions in the context of FMT to treat a complex disease-information that may provide a critical foundation for the development of more-targeted therapeutics.

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Recovery of gut microbiota of healthy adults following antibiotic exposure

Cited by 518 publications

References 71 publications

The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

Dynamic colonization of microbes and their functions after fecal microbiota transplantation for inflammatory bowel disease

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