The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

Holota, Yuliia; Dovbynchuk, Taisa; Kaji, Izumi; Vareniuk, Іgor; Dzyubenko, Natalia; Chervinska, Tetiana; Zakordonets, L.V.; Стецька, В. О.; Li, Ostapchenko; Serhiychuk, T.; Tolstanova, Ganna

doi:10.1371/journal.pone.0220642

Cited by 82 publications

(66 citation statements)

References 89 publications

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“…The observed increase in goblet cell numbers is in agreement with a previous study showing that administration the boardspectrum antibiotic ceftriaxone to Wistar rats causes increased goblet cell numbers and size (Holota et al, 2019). It is well established that bacterial colonization affects mucin gene expression, and in agreement with the present study, a negative correlation between abundance of Lactobacillus spp.…”

Section: Discussionsupporting

confidence: 93%

Short-Term Amoxicillin-Induced Perturbation of the Gut Microbiota Promotes Acute Intestinal Immune Regulation in Brown Norway Rats

et al. 2020

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The intestinal gut microbiota is essential for maintaining host health. Concerns have been raised about the possible connection between antibiotic use, causing microbiota disturbances, and the increase in allergic and autoimmune diseases observed during the last decades. To elucidate the putative connection between antibiotic use and immune regulation, we have assessed the effects of the antibiotic amoxicillin on immune regulation, protein uptake, and bacterial community structure in a Brown Norway rat model. Daily intra-gastric administration of amoxicillin resulted in an immediate and dramatic shift in fecal microbiota, characterized by a reduction of within sample (α) diversity, reduced variation between animals (β diversity), increased relative abundance of Bacteroidetes and Gammaproteobacteria, with concurrent reduction of Firmicutes, compared to a water control group. In the small intestine, amoxicillin also affected microbiota composition significantly, but in a different way than observed in feces. The small intestine of control animals was vastly dominated by Lactobacillus, but this genus was much less abundant in the amoxicillin group. Instead, multiple different genera expanded after amoxicillin administration, with high variation between individual animals, thus the small intestinal α and β diversity were higher in the amoxicillin group compared to controls. After 1 week of daily amoxicillin administration, total fecal IgA level, relative abundance of small intestinal regulatory T cells and goblet cell numbers were higher in the amoxicillin group compared to controls. Several bacterial genera, including Escherichia/Shigella, Klebsiella (Gammaproteobacteria), and Bifidobacterium, for which the relative abundance was higher in the small intestine in the amoxicillin group than in controls, were positively correlated with the fraction of small intestinal regulatory T cells. Despite of epidemiologic studies showing an association between early life antibiotic consumption and later prevalence of inflammatory bowel diseases and food allergies, our findings surprisingly indicated that amoxicillin-induced perturbation of the gut microbiota promotes acute immune regulation. We speculate that the observed increase in relative abundance of small intestinal regulatory T cells is partly mediated by immunomodulatory lipopolysaccharides derived from outgrowth of Gammaproteobacteria.

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Section: Discussionsupporting

confidence: 93%

Short-Term Amoxicillin-Induced Perturbation of the Gut Microbiota Promotes Acute Intestinal Immune Regulation in Brown Norway Rats

et al. 2020

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“…It has been reported that the impact of antibiotics on the gut microbiome can be attributed to its antimicrobial spectrum and the antimicrobial activity in the colon depending on concentrations [ 46 , 47 ]. Previous studies examined the effect of several types of antibiotics on the perturbation of gut microbiota, which may lead to an alteration in colonic mucosal homeostasis and microbial metabolites [ 18 , 27 , 48 , 49 ]. Høverstad et al reported that considerably changed SCFA profiles were observed according to the administration of ampicillin (500 mg four times daily) in the human clinical trial [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies demonstrated that the dysbiosis of the gut microbiota is linked to metabolic disease through changes to microbiota-derived metabolites, including volatile fatty acids (VFAs) via fermentation [ 17 ]. Microbial VFAs have beneficial effects in protecting intestinal epithelial barrier integrity and against intestinal inflammation [ 18 ]. In general, VFAs include a group of aliphatic monocarboxylic acids with different lengths of the chain containing from 2 to 7 carbon atoms, namely acetic (C 2 ), propionic (C 3 ), iso-butyric and butyric (C 4 ), iso-valeric and valeric (C 5 ), iso-caproic and hexanoic (C 6 ), and heptanoic (C 7 ) acids [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome

Lee

Zhu

2020

Metabolites

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Gut microbiota plays essential roles in maintaining gut homeostasis. The composition of gut microbes and their metabolites are altered in response to diet and remedial agents such as antibiotics. However, little is known about the effect of antibiotics on the gut microbiota and their volatile metabolites. In this study, we evaluated the impact of a moderate level of ampicillin treatment on volatile fatty acids (VFAs) of gut microbial cultures using an optimized real-time secondary electrospray ionization coupled with high-resolution mass spectrometry (SESI-HRMS). To evaluate the ionization efficiency, different types of electrospray solvents and concentrations of formic acid as an additive (0.01, 0.05, and 0.1%, v/v) were tested using VFAs standard mixture (C2–C7). As a result, the maximum SESI-HRMS signals of all studied m/z values were observed from water with 0.01% formic acid than those from the aqueous methanolic solutions. Optimal temperatures of sample inlet and ion chamber were set at 130 °C and 85 °C, respectively. SESI spray pressure at 0.5 bar generated the maximum intensity than other tested values. The optimized SESI-HRMS was then used for the analysis of VFAs in gut microbial cultures. We detected that the significantly elevated C4 and C7 VFAs in the headspace of gut microbial cultures six hours after ampicillin treatment (1 mg/L). In conclusion, our results suggested that the optimized SESI-HRMS method can be suitable for the analysis of VFAs from gut microbes in a rapid, sensitive, and non-invasive manner.

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“…Thus, many nano-delivery systems use pH-sensitive polymeric materials to target the microbiota with antibiotic drugs. 79,80 Synthetic polymers, including poly (acrylic acid), poly (acrylamide), poly (diethyl-aminoethyl methacrylate), poly (dimethyl-aminoethyl methacrylate), and poly (methacrylic acid), have been widely studied for the construction of pH-sensitive antibiotic nano-drugs that yield enhanced antimicrobial effects through sustained drug release. 81 Some natural polymers, including albumin and gelatin, have also been tested for the production of efficient pH-susceptible nanosystems that can improve the antimicrobial efficiency of antibiotics (i.e., ciprofloxacin, aminoglycosides) by ensuring a targeted and controlled release.…”

Section: Microbiotamentioning

confidence: 99%

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Yang¹,

Merlin²

2019

IJN

116

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Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome-dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.

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The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

Cited by 82 publications

References 89 publications

Short-Term Amoxicillin-Induced Perturbation of the Gut Microbiota Promotes Acute Intestinal Immune Regulation in Brown Norway Rats

Short-Term Amoxicillin-Induced Perturbation of the Gut Microbiota Promotes Acute Intestinal Immune Regulation in Brown Norway Rats

Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

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