scholarly journals Impact of nisin on Clostridioides difficile and microbiota composition in a fecal fermentation model of the human colon.

Author(s):  
Catherine O’Reilly ◽  
Paula O’Connor ◽  
Órla O’Sullivan ◽  
Mary C. Rea ◽  
Colin Hill ◽  
...  
2020 ◽  
Vol 76 (1) ◽  
pp. 171-178
Author(s):  
Anthony M Buckley ◽  
James Altringham ◽  
Emma Clark ◽  
Karen Bently ◽  
William Spittal ◽  
...  

Abstract Objectives The approval of new antibiotics is essential to combat infections caused by antimicrobial-resistant pathogens; however, such agents should be tested to determine their effect on the resident microbiota and propensity to select for opportunistic pathogens, such as Clostridioides difficile. Eravacycline is a new antibiotic for the treatment of complicated intra-abdominal infections. Here, we determined the effects of eravacycline compared with moxifloxacin on the microbiota and if these were conducive to induction of C. difficile infection (CDI). Methods We seeded in vitro chemostat models, which simulate the physiological conditions of the human colon, with a human faecal slurry and instilled gut-reflective concentrations of either eravacycline or moxifloxacin. Results Eravacycline instillation was associated with decreased Bifidobacterium, Lactobacillus and Clostridium species, which recovered 1 week after exposure. However, Bacteroides spp. levels decreased to below the limit of detection and did not recover prior to the end of the experiment. Post-eravacycline, a bloom of aerobic bacterial species occurred, including Enterobacteriaceae, compared with pre-antibiotic, which remained high for the duration of the experiment. These changes in microbiota were not associated with induction of CDI, as we observed a lack of C. difficile spore germination and thus no toxin was detected. Moxifloxacin exposure sufficiently disrupted the microbiota to induce simulated CDI, where C. difficile spore germination, outgrowth and toxin production were seen. Conclusions These model data suggest that, despite the initial impact of eravacycline on the intestinal microbiota, similar to clinical trial data, this novel tetracycline has a low propensity to induce CDI.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kelsea Drall ◽  
Hein Tun ◽  
Meghan B Azad ◽  
David Guttman ◽  
Malcolm Sears ◽  
...  

Abstract Objectives Colonization with Clostridioides difficile occurs in up to half of infants and is predicted by formula feeding. Although this microbe does not appear to pose any immediate risks for infants, its presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting changes in the gut microbiome that may increase opportunity for colonization of pathogenic bacteria. We explored these compositional changes in exclusively breastfed, partially breastfed and exclusively formula fed infants to describe the microbial community and C. difficile colonization in infants with distinct diets. Methods This study includes 1562 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Infants provided a fecal sample at 3–4 months of age (Mean: 3.56, SD: 1.00) which was analyzed using 16S rRNA sequencing and targeted qPCR for C. difficile. Mode of feeding was recorded in a questionnaire at a 3 month follow-up visit. C. difficile colonization was defined as positive detection (CD+) in the fecal sample (reference: not present, CD-). Multivariate association with linear models (MaAslin) was used to determine changes in microbiota composition following arsine-square root transformation of relative abundances and FDR correction. Results The prevalence of C. difficile colonization among all infants was 30.9%. Colonization rates differed among feeding groups: 22.63% of exclusively breastfed infants, 35.96% of partially breastfed infants and 49.63% of exclusively formula fed infants (P < 0.001). Microbes of the genus Bifidobacterium were decreased in CD + exclusively breastfed infants compared to non-carriers of the same diet (q = 0.02). Additionally, Blautia, Coprococcus and Clostridium, of the Lachnospiraceae family, and microbes of the Bacteroidetes phylum were of higher relative abundance (all q < 0.01) in breastfed CD + infants (both partial and exclusive). In exclusively formula fed infants, C. difficile colonization was not significantly associated with microbiota composition. Conclusions C. difficile colonization may have a dysbiotic effect on the gut microbiota composition of breastfed infants, changes which have previously been associated with childhood atopy and obesity. Funding Sources Canadian Institutes of Health Research (CIHR). AllerGen Network of Centres of Excellence (NCE)


2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Jemila C. Kester ◽  
Douglas K. Brubaker ◽  
Jason Velazquez ◽  
Charles Wright ◽  
Douglas A. Lauffenburger ◽  
...  

ABSTRACT A clinically relevant risk factor for Clostridioides difficile-associated disease (CDAD) is recent antibiotic treatment. Although broad-spectrum antibiotics have been shown to disrupt the structure of the gut microbiota, some antibiotics appear to increase CDAD risk without being highly active against intestinal anaerobes, suggesting direct nonantimicrobial effects. We examined cell biological effects of antibiotic exposure that may be involved in bacterial pathogenesis using an in vitro germfree human colon epithelial culture model. We found a marked loss of mucosal barrier and immune function with exposure to the CDAD-associated antibiotics clindamycin and ciprofloxacin, distinct from the results of pretreatment with an antibiotic unassociated with CDAD, tigecycline, which did not reduce innate immune or mucosal barrier functions. Importantly, pretreatment with CDAD-associated antibiotics sensitized mucosal barriers to C. difficile toxin activity in primary cell-derived enteroid monolayers. These data implicate commensal-independent gut mucosal barrier changes in the increased risk of CDAD with specific antibiotics and warrant further studies in in vivo systems. We anticipate this work to suggest potential avenues of research for host-directed treatment and preventive therapies for CDAD.


2017 ◽  
Vol 114 (25) ◽  
pp. 6438-6443 ◽  
Author(s):  
Jonas Cremer ◽  
Markus Arnoldini ◽  
Terence Hwa

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota.


2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Yusuke Yoshimatsu ◽  
Yohei Mikami ◽  
Takanori Kanai

AbstractThe number of patients with inflammatory bowel disease is rapidly increasing in developed countries. The main cause of this increase is thought not to be genetic, but secondary to rapidly modernized environmental change. Changes in the environment have been detrimental to enteric probiotics useful for fermentation, inducing an increase in pathobionts that survive by means other than fermentation. This dysregulated microbiota composition, the so-called dysbiosis, is believed to have increased the incidence of inflammatory bowel disease. Bacteriotherapy, a treatment that prophylactically and therapeutically corrects the composition of disturbed intestinal microbiota, is a promising recent development. In fact, fecal microbiome transplantation for recurrent Clostridioides difficile infection in 2013 was a significant contribution for bacteriotherapy. In this paper, we comprehensively review bacteriotherapy in an easy-to-understand format.


Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3020
Author(s):  
Carles Rosés ◽  
Juan Antonio Nieto ◽  
Blanca Viadel ◽  
Elisa Gallego ◽  
Ana Romo-Hualde ◽  
...  

The gut microbiota plays a key role in gastrointestinal immune and metabolic functions and is influenced by dietary composition. An in vitro protocol simulating the physiological conditions of the digestive system helps to study the effects of foods/biocompounds on gut microbiome and metabolome. The Dynamic-Colonic Gastrointestinal Digester consists of five interconnected compartments, double jacket vessels that simulate the physiological conditions of the stomach, the small intestine and the three colonic sections, which are the ascending colon, transverse colon and descending colon. Human faeces are required to reproduce the conditions and culture medium of the human colon, allowing the growth of the intestinal microbiota. After a stabilization period of 12 days, a food/biocompound can be introduced to study its modulatory effects during the next 14 days (treatment period). At the end of the stabilization and treatment period, samples taken from the colon compartments are analysed. The 16S rRNA gene analysis reveals the microbiota composition. The untargeted metabolomics analysis gives more than 10,000 features (metabolites/compounds). The present protocol allows in vitro testing of the modulatory effects of foods or biocompounds on gut microbiota composition and metabolic activity.


2015 ◽  
Vol 5 ◽  
Author(s):  
Arancha Hevia ◽  
David Bernardo ◽  
Enrique Montalvillo ◽  
Hafid O. Al-Hassi ◽  
Luis Fernández-Salazar ◽  
...  

2020 ◽  
Vol 8 (5) ◽  
pp. 677 ◽  
Author(s):  
Monique J. T. Crobach ◽  
Quinten R. Ducarmon ◽  
Elisabeth M. Terveer ◽  
Celine Harmanus ◽  
Ingrid M. J. G. Sanders ◽  
...  

Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). Therefore, gut microbiota composition from patients with CDC (n = 41), with CDI (n = 41), and without CDC (controls, n = 43) was determined through 16S rRNA gene amplicon sequencing. Bacterial diversity was decreased in CDC and CDI patients (p < 0.01). Overall microbiota composition was significantly different between control, CDC, and CDI patients (p = 0.001). Relative abundance of Clostridioides (most likely C. difficile) increased stepwise from controls to CDC and CDI patients. In addition, differential abundance analysis revealed that CDI patients’ gut microbiota was characterized by significantly higher relative abundance of Bacteroides and Veillonella than CDC patients and controls. Control patients had significantly higher Eubacterium hallii and Fusicatenibacter abundance than colonized patients. Network analysis indicated that Fusicatenibacter was negatively associated with Clostridioides in CDI patients, while Veillonella was positively associated with Clostridioides in CDC patients. Bacterial microbiota diversity decreased in both CDC and CDI patients, but harbored a distinct microbiota. Eubacterium hallii and Fusicatenibacter may indicate resistance against C. difficile colonization and subsequent infection, while Veillonella may indicate susceptibility to colonization and infection by C. difficile.


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