scholarly journals Antibiotic-induced rat gut microbiota dysbiosis and salmonella resistance

2021 ◽  
Vol 2 (4/S) ◽  
pp. 93-100
Author(s):  
Begzod Shokirov ◽  
Yulduz Halimova

Antibiotics are the most common medicines used to treat human infectious diseases. Based on their chemical structure, antibiotics mainly include the following categories: quinolones, β-lactams, macrolides, and aminoglycosides among others. The mechanism of different antibiotics varies, and there are four main mechanisms: inhibition of bacterial cell wall synthesis, interaction with cell membranes, interference with protein synthesis, and inhibition of nucleic acid replication and transcription. Antibiotics can act on pathogenic bacteria. Accordingly, antibiotics can also affect normal bacteria that colonize the human body. The size, structure, and function of the microbiota may change in response to antibiotic treatment. Significant changes in the human gut microbiota may be associated with repeated use of antibiotics [3]; in the following days, these changes were restored. However, little is known about comparing the response of the gut microbiota to antibiotic treatment. Probiotics are beneficial to the host when administered in adequate amounts. Lactobacillus rhamnosus was one of the most common probiotics studied by scientists regarding its culture, function, and metabolism [10]. However, the effect of L. rhamnosus present in the gut microbiota on the host's susceptibility to pathogenic bacteria after taking antibiotics has rarely been discussed. In our current study, rats were given two types of antibiotics, namely vancomycin and ampicillin, and their oral and intestinal microbiota was observed at 3 time points.  The rats were treated with antibiotics or L. rhamnosus, and then infected with Salmonella entericaserovarTyphimurium (S. Typhimurium ) via a gastric tube. Fecal samples were then collected to determine the pathogenic load. Ampicillin and vancomycin act in different antimicrobial spectra and have different absorption in the digestive tract. In addition, the concentration of these antibiotics entering the digestive tract varies; these factors can affect the host microbiota. Thus, this study aimed to compare the effects of these antibiotics on the gut microbiota at normal doses, as well as to evaluate the differences in the results. The gut microbiota underwent dramatic changes during the administration period. Changes in the gut microbiota affected the host's susceptibility to pathogens when infected with bacteria due to changes in resistance to colonization.

2021 ◽  
Author(s):  
Wenjing Peng ◽  
Hui Li ◽  
Xiaole Zhao ◽  
Bing Shao ◽  
Kui Zhu

Abstract Background: Natural and synthetic phenazines are ubiquitously occurred in environment and have been used for various therapeutic purposes in human, animals and agriculture, and the widespread use makes residue problem in environment and foods increasingly serious. However, the metabolic and comprehensive impacts of phenazines on the digestive tract are poorly understood, particularly the microbial pyocyanin (PYO), the most representative phenazines produced by Pseudomonas . Here, we utilized PYO as the representative of phenazines to study the effects on digestive tract. Results: Metabolic kinetic analysis showed that PYO exhibited low oral bioavailability in both rats and swine model, revealing a restriction of PYO in gut and might cause impacts on digestive tract. PYO was subsequently found to induce intestinal barrier destruction including inflammation and reactive oxygen species (ROS) accumulation in duodenum. Microbiome analysis showed that PYO caused gut microbiota dysbiosis by decreasing the symbiotic bacteria and increasing the opportunistic pathogenic bacteria. Additionally, the integral and dysfunctional assessment of liver demonstrated that PYO induced liver inflammation and metabolic disorder. Metabolism analysis further confirmed that PYO could be metabolized by both gut microbiota and liver, and all metabolites retained the nitrogen-containing tricyclic structural skeleton of phenazines, which was the core bioactivity of phenazine compounds, indicating all the outcomes were due to the intrinsic characteristic of phenazine structure. Conclusions: PYO were low oral bioavailable and all the metabolites retained the nitrogen-containing tricyclic structural skeleton, final resulting in the damages to digestive tract including intestinal barrier destruction, gut microbiota dysbiosis, liver damages and metabolic disorder. These findings elucidated the effect of phenazines on digestive tract in vivo and shed light on the rational design of phenazines for the development and application of such compounds in future.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Debra Poutsiaka ◽  
Lori Stern ◽  
Virginia Riquelme ◽  
Emily Hollister ◽  
Julia Cope ◽  
...  

Abstract Objectives This exploratory study builds upon an earlier study of probiotic supplementation1 to assess the effects of a probiotic combination (P) of LGG and BB-12 on human gut microbiota composition and function, and to uncover an association with BMI. Methods Healthy subjects ingested P for 21 days (n = 18, P group) or did not (n = 7, C group). Fecal samples obtained at baseline (D_0) and after 21 days of supplementation (D_21) underwent 16S ribosomal RNA gene and shotgun metagenomics sequencing to characterize the bacterial and archaeal communities to the genus/species level and identify functional community genes. Results Following P ingestion, no global differences in microbiota community structure or relative gene abundance were detected. In targeted analyses, the abundances of LGG and BB-12 in the P group at D_21 increased in a statistically significant manner as the BMI decreased (Spearman correlation, P = 0.04 and P = 0.01, respectively). The relative abundance of LGG but not BB-12 appeared increased in P subjects at D_21 with BMI < 25 compared to BMI > 25 (P = 0.09). P group subjects with BMI < 25 demonstrated trends toward or statistically significant increases in the relative abundances of 5 genes involved with flagellar structure (KEGG orthologs K02422, P = 0.04; K03406, P = 0.06; K02407, P = 0.08; K02397, P = 0.08; K02396, P = 0.09) at D_21 compared to those with BMI > 25. No such differences were observed for the C group nor were there differences in relative gene abundance at D_0 in the P group with BMI < 25 vs BMI > 25. Conclusions We observed no global changes in the fecal microbial community structure or function with P ingestion in this sample of healthy persons. However, we did observe patterns suggestive of a potential link between BMI and the response of the gut microbiota to P. Although our results are based on a small number of subjects, they are in line with previous findings related to LGG supplementation and the expression of flagellar genes2. We agree with other recent reports that future studies would benefit from a detailed examination of the transcriptome, proteome and/or metabolome to better understand the potential impact of probiotics on the gut microbiota, and the mechanism of the effect of BMI. Funding Sources Pfizer Inc.


Author(s):  
Isaac Raplee ◽  
Lacey Walker ◽  
Lei Xu ◽  
Anil Surathu ◽  
Ashok Chockalingam ◽  
...  

Abstract Introduction According to the Centers for Disease Control’s 2015 Hospital Acquired Infection Hospital Prevalence Survey, 1 in 31 hospital patients was infected with at least one nosocomial pathogen while being treated for unrelated issues. Many studies associate antibiotic administration with nosocomial infection occurrence. However, to our knowledge, there is little to no direct evidence of antibiotic administration selecting for nosocomial opportunistic pathogens. Aim This study aims to confirm gut microbiota shifts in an animal model of antibiotic treatment to determine whether antibiotic use favors pathogenic bacteria. Methodology We utilized next-generation sequencing and in-house metagenomic assembly and taxonomic assignment pipelines on the fecal microbiota of a urinary tract infection mouse model with and without antibiotic treatment. Results Antibiotic therapy decreased the number of detectable species of bacteria by at least 20-fold. Furthermore, the gut microbiota of antibiotic treated mice had a significant increase of opportunistic pathogens that have been implicated in nosocomial infections, like Acinetobacter calcoaceticus/baumannii complex, Chlamydia abortus, Bacteroides fragilis, and Bacteroides thetaiotaomicron. Moreover, antibiotic treatment selected for antibiotic resistant gene enriched subpopulations for many of these opportunistic pathogens. Conclusions Oral antibiotic therapy may select for common opportunistic pathogens responsible for nosocomial infections. In this study opportunistic pathogens present after antibiotic therapy harbored more antibiotic resistant genes than populations of opportunistic pathogens before treatment. Our results demonstrate the effects of antibiotic therapy on induced dysbiosis and expansion of opportunistic pathogen populations and antibiotic resistant subpopulations of those pathogens. Follow-up studies with larger samples sizes and potentially controlled clinical investigations should be performed to confirm our findings.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Guo ◽  
Wenye Geng ◽  
Shan Chen ◽  
Li Wang ◽  
Xuli Rong ◽  
...  

The effects of ginger on gastrointestinal disorders such as ulcerative colitis have been widely investigated using experimental models; however, the mechanisms underlying its therapeutic actions are still unknown. In this study, we investigated the correlation between the therapeutic effects of ginger and the regulation of the gut microbiota. We used dextran sulfate sodium (DSS) to induce colitis and found that ginger alleviated colitis-associated pathological changes and decreased the mRNA expression levels of interleukin-6 and inducible nitric oxide synthase in mice. 16s rRNA sequencing analysis of the feces samples showed that mice with colitis had an intestinal flora imbalance with lower species diversity and richness. At the phylum level, a higher abundance of pathogenic bacteria, Proteobacteria and firmicutes, were observed; at the genus level, most samples in the model group showed an increase in Lachnospiraceae_NK4A136_group. The overall analysis illustrated an increase in the relative abundance of Lactobacillus_murinus, Lachnospiraceae_bacterium_615, and Ruminiclostridium_sp._KB18. These increased pathogenic bacteria in model mice were decreased when treated with ginger. DSS-treated mice showed a lower abundance of Muribaculaceae, and ginger corrected this disorder. The bacterial community structure of the ginger group analyzed with Alpha and Beta indices was similar to that of the control group. The results also illustrated that altered intestinal microbiomes affected physiological functions and adjusted key metabolic pathways in mice. In conclusion, this research presented that ginger reduced DSS-induced colitis severity and positively regulated the intestinal microbiome. Based on the series of data in this study, we hypothesize that ginger can improve diseases by restoring the diversity and functions of the gut microbiota.


2019 ◽  
Author(s):  
Maria Guirro ◽  
Andrea Costa ◽  
Andreu Gual-Grau ◽  
Pol Herrero ◽  
Helena Torrell ◽  
...  

AbstractObesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Recently, the gut microbiota has emerged as a new potential therapeutic target for the treatment of obesity. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent a strategy for obesity treatment. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function.To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as an obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption.


2020 ◽  
Vol 26 (11) ◽  
pp. 1636-1647
Author(s):  
Xiaojun Zhuang ◽  
Zhenyi Tian ◽  
Rui Feng ◽  
Manying Li ◽  
Tong Li ◽  
...  

Abstract Background Gut microbiota dysbiosis is associated with the occurrence and development of Crohn disease (CD). Currently, infliximab (IFX) is used more and more to treat CD; however, gut microbiota alterations during IFX therapy are variable and sometimes even contradictory. We longitudinally identified microbial changes during IFX therapy associated with the clinical and endoscopic response to IFX treatment in CD. Methods Fecal-associated microbiota was analyzed using 16S sequencing in 49 patients with active CD who were prospectively recruited at baseline, week 6, and week 30, respectively. Moreover, a model trained on the gut microbiota alterations at week 6 was developed to investigate their potential to predict clinical and endoscopic responses to IFX therapy at weeks 14 and 30. Results Characteristics of fecal microbiota composition in patients with CD after IFX treatment displayed an increased diversity and richness, a significant gain in short-chain fatty acid -producing bacteria, and a loss of pathogenic bacteria. Furthermore, certain functional profiles of Kyoto Encyclopedia of Genes and Genomes pathways were predictably altered during the treatment period. Increased proportions of Lachnospiraceae and Blautia were associated with IFX efficacy; the combined increase of these taxa at week 6 showed 83.4% and 84.2% accuracy in predicting clinical response at weeks 14 and 30, respectively, with a predictive value of 89.1% in predicting endoscopic response at week 30. Conclusions We found that IFX diminished CD-related gut microbial dysbiosis by modifying microbiota composition and function. Specifically, increased Lachnospiraceae and Blautia at week 6 are associated with the clinical and endoscopic response to IFX, providing potentially predictive biomarkers for IFX treatment decision-making.


2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Huihui Xu ◽  
Hongyan Zhao ◽  
Danping Fan ◽  
Meijie Liu ◽  
Jinfeng Cao ◽  
...  

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases caused by abnormal immune activation and immune tolerance. Immunomodulatory cells (ICs) play a critical role in the maintenance and homeostasis of normal immune function and in the pathogenesis of RA. The human gastrointestinal tract is inhabited by trillions of commensal microbiota on the mucosal surface that play a fundamental role in the induction, maintenance, and function of the host immune system. Gut microbiota dysbiosis can impact both the local and systemic immune systems and further contribute to various diseases, such as RA. The neighbouring intestinal ICs located in distinct intestinal mucosa may be the most likely intermediary by which the gut microbiota can affect the occurrence and development of RA. However, the reciprocal interaction between the components of the gut microbiota and their microbial metabolites with distinct ICs and how this interaction may impact the development of RA are not well studied. Therefore, a better understanding of the gut microbiota, ICs, and their interactions might improve our knowledge of the mechanisms by which the gut microbiota contribute to RA and facilitate the further development of novel therapeutic approaches. In this review, we have summarized the roles of the gut microbiota in the immunopathogenesis of RA, especially the interactions between the gut microbiota and ICs, and further discussed the strategies for treating RA by targeting/regulating the gut microbiota.


2018 ◽  
Vol 243 (7) ◽  
pp. 613-620 ◽  
Author(s):  
Yi Lyu ◽  
Lei Wu ◽  
Fang Wang ◽  
Xinchun Shen ◽  
Dingbo Lin

Dysbiosis, a broad spectrum of imbalance of the gut microbiota, may progress to microbiota dysfunction. Dysbiosis is linked to some human diseases, such as inflammation-related disorders and metabolic syndromes. However, the underlying mechanisms of the pathogenesis of dysbiosis remain elusive. Recent findings suggest that the microbiome and gut immune responses, like immunoglobulin A production, play critical roles in the gut homeostasis and function, and the progression of dysbiosis. In the past two decades, much progress has been made in better understanding of production of immunoglobulin A and its association with commensal microbiota. The present minireview summarizes the recent findings in the gut microbiota dysbiosis and dysfunction of immunoglobulin A induced by the imbalance of pathogenic bacteria and commensal microbiota. We also propose the potentials of dietary carotenoids, such as β-carotene and astaxanthin, in the improvement of the gut immune system maturation and immunoglobulin A production, and the consequent promotion of the gut health. Impact statement The concept of carotenoid metabolism in the gut health has not been well established in the literature. Here, we review and discuss the roles of retinoic acid and carotenoids, including pro-vitamin A carotenoids and xanthophylls in the maturation of the gut immune system and IgA production. This is the first review article about the carotenoid supplements and the metabolites in the regulation of the gut microbiome. We hope this review would provide a new direction for the management of the gut microbiota dysbiosis by application of bioactive carotenoids and the metabolites.


mSystems ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Yue O. O. Hu ◽  
Luisa W. Hugerth ◽  
Carina Bengtsson ◽  
Arlisa Alisjahbana ◽  
Maike Seifert ◽  
...  

ABSTRACTSalmonellainfection is one of the main causes of food-borne diarrheal diseases worldwide. Although mostSalmonellainfections can be cleared without treatment, some cause serious illnesses that require antibiotic treatment. In view of the growing emergence of antibiotic-resistantSalmonellastrains, novel treatments are increasingly required. Furthermore, there is a striking paucity of data on how a balanced human gut microbiota responds toSalmonellainfection. This study aimed to evaluate whether a balanced gut microbiota protects againstSalmonellagrowth and to compare two antimicrobial approaches for managingSalmonellainfection: bacteriophage (phage) treatment and antibiotic treatment. Anaerobically cultivated human intestinal microflora (ACHIM) is a feasible model for the human gut microbiota and naturally inhibitsSalmonellainfection. By mimickingSalmonellainfectionin vitrousing ACHIM, we observed a large reduction ofSalmonellagrowth by the ACHIM itself. Treatments with phage and antibiotic further inhibitedSalmonellagrowth. However, phage treatment had less impact on the nontargeted bacteria in ACHIM than the antibiotic treatment did. Phage treatment has high specificity when combatingSalmonellainfection and offers a noninvasive alternative to antibiotic treatment.IMPORTANCEAntibiotic-resistant bacteria are a global threat. Therefore, alternative approaches for combatting bacteria, especially antibiotic-resistant bacteria, are urgently needed. Using a human gut microbiota model, we demonstrate that bacteriophages (phages) are able to substantially decrease pathogenicSalmonellawithout perturbing the microbiota. Conversely, antibiotic treatment leads to the eradication of close to all commensal bacteria, leaving only antibiotic-resistant bacteria. An unbalanced microbiota has been linked to many diseases both in the gastrointestinal tract or “nonintestinal” diseases. In our study, we show that the microbiota provides a protective effect againstSalmonella. Since phage treatment preserves the healthy gut microbiota, it is a feasible superior alternative to antibiotic treatment. Furthermore, when combating infections caused by pathogenic bacteria, gut microbiota should be considered.


2021 ◽  
Vol 9 (6) ◽  
pp. 1288
Author(s):  
Xiaoli Chen ◽  
Huadong Yi ◽  
Shuang Liu ◽  
Yong Zhang ◽  
Yuqin Su ◽  
...  

Eating disorders are directly or indirectly influenced by gut microbiota and innate immunity. Probiotics have been shown to regulate gut microbiota and stimulate immunity in a variety of species. In this study, three kinds of probiotics, namely, Lactobacillus plantarum, Lactobacillus rhamnosus and Clostridium butyricum, were selected for the experiment. The results showed that the addition of three probiotics at a concentration of 108 colony forming unit/mL to the culture water significantly increased the ratio of the pellet feed recipients and survival rate of mandarin fish (Siniperca chuatsi) under pellet-feed feeding. In addition, the three kinds of probiotics reversed the decrease in serum lysozyme and immunoglobulin M content, the decrease in the activity of antioxidant enzymes glutathione and catalase and the decrease in the expression of the appetite-stimulating regulator agouti gene-related protein of mandarin fish caused by pellet-feed feeding. In terms of intestinal health, the three probiotics reduced the abundance of pathogenic bacteria Aeromonas in the gut microbiota and increased the height of intestinal villi and the thickness of foregut basement membrane of mandarin fish under pellet-feed feeding. In general, the addition of the three probiotics can significantly improve eating disorders of mandarin fish caused by pellet feeding.


Sign in / Sign up

Export Citation Format

Share Document