Long-term impacts of antibiotic exposure on the human intestinal microbiota

Jernberg, Cecilia; Löfmark, Sonja; Edlund, Charlotta; Jansson, Janet

doi:10.1099/mic.0.040618-0

Cited by 901 publications

(705 citation statements)

References 48 publications

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“…Resistance to a pathogenic bacterium is mostly determined by the past infection-history of a patient; eventually, resistance to some targeted or non-targeted pathogen might be more likely [27] . Secondly, because of simple and plastic genomes of bacteria, the emergence of resistant mutants for a class of antibiotics due to one used from that class is more likely than imagined, at least for the chance factor.…”

Section: Discussionmentioning

confidence: 99%

Surveillance of multidrug resistant uropathogenic bacteria in hospitalized patients in Indian

Mishra

Debata

Padhy

2013

Asian Pacific Journal of Tropical Biomedicine

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Objective: To record surveillance, antibiotic resistance of uropathogens of hospitalized patients over a period of 18 months. Methods: Urine samples from wards and cabins were used for isolating urinary tract infection (UTI)-causing bacteria that were cultured on suitable selective media and identified by biochemical tests; and their antibiograms were ascertained by KirbyBauer's disc diffusion method, in each 6-month interval of the study period, using 18 antibiotics of five different classes. Results: From wards and cabins, 1 245 samples were collected, from which 996 strains of bacteria belonging to 11 species were isolated, during April 2011 to September 2012. Two Gram-positive, Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), and nine Gram-negative bacteria, Acinetobacter baumannii, Citrobacter sp., Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were isolated. Both S. aureus and E. faecalis were vancomycin resistant, and resistant-strains of all pathogens increased in each 6-month period of study. Particularly, all Gram-negatives were resistant to nitrofurantoin and co-trimoxazole, the most preferred antibiotics of empiric therapy for UTI. Conclusions: Antibiograms of 11 UTIcausing bacteria recorded in this study indicated moderately higher numbers of strains resistant to each antibiotic studied, generating the fear of precipitating fervent episodes in public health particularly with bacteria, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and S. aureus. Moreover, vancomycin resistance in strains of S. aureus and E. faecalis is a matter of concern.

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Section: Discussionmentioning

confidence: 99%

Surveillance of multidrug resistant uropathogenic bacteria in hospitalized patients in Indian

Mishra

Debata

Padhy

2013

Asian Pacific Journal of Tropical Biomedicine

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“…5 These antibiotics were chosen due to the broad spectrum capacity and well documented impacts on intestinal microbiota. 17 Animals were allowed to drink ad libitum for the duration of the experiment with water replacement at 3 day intervals. A probiotic blend of L. rhamnosus A 191, Lactobacillus acidophilus, Bifidobacterium breve, Bifidobacterium longum (CVS Maximum Strength Probiotic) were resuspended in 5mls PBS for a total of 4 billion organisms per milliliter.…”

Section: Methodsmentioning

confidence: 99%

Impact of probiotic supplements on microbiome diversity following antibiotic treatment of mice

2016

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Shifts in microbial populations of the intestinal tract have been associated with a multitude of nutritional, autoimmune, and infectious diseases. The limited diversity following antibiotic treatments creates a window for opportunistic pathogens, diarrhea, and inflammation as the microbiome repopulates. Depending on the antibiotics used, microbial diversity can take weeks to months to recover. To alleviate this loss of diversity in the intestinal microbiota, supplementation with probiotics has become increasingly popular. However, our understanding of the purported health benefits of these probiotic bacteria and their ability to shape the microbiome is significantly lacking. This study examined the impact of probiotics concurrent with antibiotic treatment or during the recovery phase following antibiotic treatment of mice. We found that probiotics did not appear to colonize the intestine themselves or shift the overall diversity of the intestinal microbiota. However, the probiotic supplementation did significantly change the types of bacteria which were present. In particular, during the recovery phase the probiotic caused a suppression of Enterobacteriaceae outgrowth (Shigella and Escherichia) while promoting a blooming of Firmicutes, particularly from the Anaerotruncus genus. These results indicate that probiotics have a significant capacity to remodel the microbiome of an individual recovering from antibiotic therapy.

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“…Members of the Lactobacillales are major beneficial members of the gut microbiome community. There are serious consequences that arise from the elimination of these bacteria when broad-spectrum antibiotics are deployed (75)(76)(77). However, FASII inhibitors may not affect this community, making these agents desirable for the treatment of susceptible pathogens such as S. aureus.…”

Section: Summary and Future Questionsmentioning

confidence: 99%

How Bacterial Pathogens Eat Host Lipids: Implications for the Development of Fatty Acid Synthesis Therapeutics

Yao

Rock

2015

Journal of Biological Chemistry

107

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Bacterial type II fatty acid synthesis (FASII) is a target for the development of novel therapeutics. Bacteria incorporate extracellular fatty acids into membrane lipids, raising the question of whether pathogens use host fatty acids to bypass FASII and defeat FASII therapeutics. Some pathogens suppress FASII when exogenous fatty acids are present to bypass FASII therapeutics. FASII inhibition cannot be bypassed in many bacteria because essential fatty acids cannot be obtained from the host. FASII antibiotics may not be effective against all bacteria, but a broad spectrum of Gram-negative and -positive pathogens can be effectively treated with FASII inhibitors. The Biological ProblemThe discovery of antibiotics for the treatment of infectious bacterial diseases has led to significant improvements in human health. The success of these broad-spectrum "miracle drugs" is reflected in the dearth of new antibiotic classes introduced in the last 30 years (1). However, the steady increase in bacterial antibiotic resistance to all antimicrobials in clinical use (2, 3) has caused infectious bacterial diseases to re-emerge as a serious threat to human health. These resistant bacteria are a clear and present danger that will require the discovery of new antibiotic targets and drugs to combat (4). Fatty acid synthesis is a vital facet of bacterial physiology, and its essentiality for membrane formation makes it an attractive target for drug discovery (5). Nature has exploited this dependence to produce a variety of natural products that target bacterial fatty acid synthesis (5-7). Selective targeting of the bacterial pathway is possible due to the significant differences in the structure of eukaryotic and bacterial fatty acid synthesis systems. Mammalian type I fatty acid synthase is a large, multifunctional peptide that elongates acetyl-CoA to produce a single product, palmitic acid (8).In the bacterial type II system (FASII), 2 each enzymatic step is carried out by a discrete, monofunctional enzyme ( Fig. 1) (9).Many inhibitors targeting FASII enzymes have been made in the past two decades, and several of these inhibitors are effective antibiotics both in vitro and in animal models (10 -13). Two of these compounds, AFN-1252 and CG400549, have proven efficacy in human clinical trials, providing direct evidence that targeting FASII components can result in effective therapeutic agents (14,15).Most bacteria are able to incorporate extracellular fatty acids into their membrane phospholipids, leading to the important question of whether this property will allow them to circumvent FASII inhibitors by acquiring the fatty acids they need from the host. Brinster et al. (16) argued that FASII is not an antibacterial target in Gram-positive bacteria due to the ability of Streptococcus agalactiae to circumvent FASII inhibitors when supplied with exogenous host-derived fatty acids. However, the situation is more complex because not all Gram-positive bacteria have the same fatty acid structures as mammals, and the conclusion is not co...

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Long-term impacts of antibiotic exposure on the human intestinal microbiota

Cited by 901 publications

References 48 publications

Surveillance of multidrug resistant uropathogenic bacteria in hospitalized patients in Indian

Surveillance of multidrug resistant uropathogenic bacteria in hospitalized patients in Indian

Impact of probiotic supplements on microbiome diversity following antibiotic treatment of mice

How Bacterial Pathogens Eat Host Lipids: Implications for the Development of Fatty Acid Synthesis Therapeutics

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