Antibiotic Therapy and the Gut Microbiome: Investigating the Effect of Delivery Route on Gut Pathogens

Author(s):  
Stephen A. Kelly ◽  
Jonathan Nzakizwanayo ◽  
Aoife M. Rodgers ◽  
Li Zhao ◽  
Rebecca Weiser ◽  
...  
Author(s):  
Paola I. Bonilla-Carrero ◽  
Hannah Mader ◽  
Nathan Meier ◽  
Isis Olivas ◽  
Bridget Boyle ◽  
...  

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Tungadri Bose ◽  
K. V. Venkatesh ◽  
Sharmila S. Mande

Abstract Background In 2017, World Health Organization (WHO) published a catalogue of 12 families of antibiotic-resistant “priority pathogens” that are posing the greatest threats to human health. Six of these dreaded pathogens are known to infect the human gastrointestinal system. In addition to causing gastrointestinal and systemic infections, these pathogens can also affect the composition of other microbes constituting the healthy gut microbiome. Such aberrations in gut microbiome can significantly affect human physiology and immunity. Identifying the virulence mechanisms of these enteric pathogens are likely to help in developing newer therapeutic strategies to counter them. Results Using our previously published in silico approach, we have evaluated (and compared) Host-Pathogen Protein-Protein Interaction (HPI) profiles of four groups of enteric pathogens, namely, different species of Escherichia, Shigella, Salmonella and Vibrio. Results indicate that in spite of genus/ species specific variations, most enteric pathogens possess a common repertoire of HPIs. This core set of HPIs are probably responsible for the survival of these pathogen in the harsh nutrient-limiting environment within the gut. Certain genus/ species specific HPIs were also observed. Conslusions The identified bacterial proteins involved in the core set of HPIs are expected to be helpful in understanding the pathogenesis of these dreaded gut pathogens in greater detail. Possible role of genus/ species specific variations in the HPI profiles in the virulence of these pathogens are also discussed. The obtained results are likely to provide an opportunity for development of novel therapeutic strategies against the most dreaded gut pathogens.


2021 ◽  
Author(s):  
Laura M. Chambers ◽  
Emily Esakov ◽  
Chad Braley ◽  
Lexie Trestan ◽  
Zahraa Alali ◽  
...  

Abstract Background: Epithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections, although this profoundly impacts the gut microbiome. Multiple studies suggest that an unperturbed gut microbiome may provide a protective microenvironment, and disruption may be permissive to tumor growth and chemotherapy resistance, including platinum agents. Experimental Design: We assessed whether antibiotic therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given control or antibiotic (ABX) containing water (metronidazole, ampicillin, vancomycin, and neomycin) for two weeks before being intraperitoneally injected with murine ID8 or ID8-VEGF EOC cells. Tumors were monitored and cisplatin therapy was administered weekly until endpoint. Stool was collected throughout the study to assess for microbial population effects over time. Cecal microbiota transplants (CMTs) of contents derived from ABX or control treated donor mice were performed on ABX treated recipient mice. Results: Both immune competent and immune compromised ID8 and ID8 VEGF tumor-bearing mice demonstrated a decreased response to cisplatin therapy in ABX treated groups with an increase in overall tumor burden. RNAseq analysis showed enrichment of multiple cell proliferation and stem cell pathways, and stem cell genes SOX2, WNT and PAX2. The self-renewal of cancer cells derived from tumors of ABX treated mice was increased compared to tumors from control mice, indicative of a microbiota derived tumor suppressor. Conclusion: Collectively, these studies indicate an intact microbiome provides a tumor suppressor and maintains chemosensitivity that is disrupted by ABX treatment.


2020 ◽  
Vol 21 (11) ◽  
Author(s):  
Madiyar Nurgaziyev ◽  
YERMEK AITENOV ◽  
ZHANAGUL KHASSENBEKOVA ◽  
SANIYA AKPANOVA ◽  
KAIRAT RYSBEKOV ◽  
...  

Abstract. Nurgaziyev M, Atenov Y, Khassenbekova Z, Akpanova S, Rysbekov K, Kozhakhmetov S, Nurgozhina A, Sergazy S, Chulenbayeva L, Ospanova Z, Tuyakova A, Mukhambetganov N, Sattybayeva R, Urazova S, Galymgozhina N, Zhumadilova A, Gulyaev A, Kushugulova A. 2020. Effect of mare’s milk prebiotic supplementation on the gut microbiome and the immune system following antibiotic therapy. Biodiversitas 21: 5065-5071. Antibiotic treatment can severely affect the gut microbiome for short-term and long-term consequences. Probiotic and prebiotic supplements are widely prescribed to modulate the composition and function of the human gut microbiome. The current study aims to determine the impacts of mare’s milk prebiotics on the diversity of gut bacterial communities and the local immune system when administered during and after a course of antibiotic therapy. Six children aged 4 to 5 years diagnosed with bilateral bronchopneumonia were prescribed cephalosporin (cefuroxime) antibiotics. During the 60 days of the study, three children consumed mare’s milk prebiotics, while the other three did not. Fecal samples were collected daily during antibiotic therapy and every five days after the last day of antibiotic treatment. Total DNA was isolated, and the taxonomic composition of the gut microbiome was analyzed by sequencing the 16S rRNA gene (V1-V3 region). The MULTIPLEX MAP platform was used to evaluate the local immune status. The relative abundance of 11 genera was reduced and did not recover until the last day of the study. The abundance of Bacteroides was not significantly altered in either group. Christensenella, Rothia, Abiotrophia, Acinetobacter, Anaerotruncus, Holdemania, and Turicibacter numbers were significantly increased on day five and remained at the same level during the study period. Cephalosporin administration also reduced the levels of pro-inflammatory and anti-inflammatory cytokines/chemokines (MIP1α, TNFα, GMCSF, GCSF, sCD40L, FGF2, TGFα, IL1α, and IP10).


Microbiome ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Rabia Maqsood ◽  
Rachel Rodgers ◽  
Cynthia Rodriguez ◽  
Scott A. Handley ◽  
I. Malick Ndao ◽  
...  

Abstract Background The earliest microbial colonizers of the human gut can have life-long consequences for their hosts. Precisely how the neonatal gut bacterial microbiome and virome are initially populated is not well understood. To better understand how the maternal gut microbiome influences acquisition of the infant gut microbiome, we studied the early life bacterial microbiomes and viromes of 28 infant twin pairs and their mothers. Results Infant bacterial and viral communities more closely resemble those of their related co-twin than unrelated infants. We found that 63% of an infant’s bacterial microbiome can be traced to their mother’s gut microbiota. In contrast, only 15% of their viral communities are acquired from their mother. Delivery route did not determine how much of the bacterial microbiome or virome was shared from mother to infant. However, bacteria-bacteriophage interactions were altered by delivery route. Conclusions The maternal gut microbiome significantly influences infant gut microbiome acquisition. Vertical transmission of the bacterial microbiome is substantially higher compared to vertical transmission of the virome. However, the degree of similarity between the maternal and infant gut bacterial microbiome and virome did not vary by delivery route. The greater similarity of the bacterial microbiome and virome between twin pairs than unrelated twins may reflect a shared environmental exposure. Thus, differences of the inter-generation transmissibility at birth between the major kingdoms of microbes indicate that the foundation of these microbial communities are shaped by different rules.


2020 ◽  
Author(s):  
Laura M. Chambers ◽  
Emily L. Esakov ◽  
Chad Braley ◽  
Lexie Trestan ◽  
Zahraa Alali ◽  
...  

AbstractBackgroundEpithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections, although this profoundly impacts the gut microbiome. Multiple studies suggest that an unperturbed gut microbiome may provide a protective microenvironment, and disruption may be permissive to tumor growth and chemotherapy resistance, including platinum agents.Experimental DesignWe assessed whether antibiotic therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given either metronidazole, ampicillin, vancomycin, and neomycin (ABX) containing or control water for two weeks before being intraperitoneally injected with murine ID8 or ID8-VEGF EOC cells. Tumors were monitored and cisplatin therapy was administered weekly until endpoint. Stool was collected throughout the study to asses for microbial population effects over time.ResultsBoth immune competent and immune compromised ID8 and ID8 VEGF tumor-bearing mice demonstrated a decreased response to cisplatin therapy in ABX treated groups with an increase in overall tumor burden. RNAseq analysis showed enrichment of multiple cell proliferation and stem cell pathways, and stem cell genes SOX2, WNT and PAX2. The self-renewal of ABX treated tumor cells was also increased.ConclusionCollectively, these studies indicate an intact microbiome provides a tumor suppressive microenvironment and enhances sensitivity to cisplatin.


Gut Pathogens ◽  
2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Dachao Liang ◽  
Ross Ka‑Kit Leung ◽  
Wenda Guan ◽  
William W. Au

Following publication of the original article in Gut Pathogens [1], it was brought to our attention that Dr. Ross Ka Kit Leung’s affiliation was incomplete. Dr. Leung is appointed as an Adjunct Professor of Guangzhou Medical University from January 1st 2017 to December 31st 2019. He would like to correct here the affiliation and acknowledge his role at the Guangzhou Medical University when this article was published.


2020 ◽  
Author(s):  
Laura Chambers ◽  
Emily Esakov ◽  
Chad Braley ◽  
Lexie Trestan ◽  
Zahraa Alali ◽  
...  

Abstract Background: Epithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections, although this profoundly impacts the gut microbiome. Multiple studies suggest that an unperturbed gut microbiome may provide a protective microenvironment, and disruption may be permissive to tumor growth and chemotherapy resistance, including platinum agents. Experimental Design: We assessed whether antibiotic therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given either metronidazole, ampicillin, vancomycin, and neomycin (ABX) containing or control water for two weeks before being intraperitoneally injected with murine ID8 or ID8-VEGF EOC cells. Tumors were monitored and cisplatin therapy was administered weekly until endpoint. Stool was collected throughout the study to asses for microbial population effects over time.Results: Both immune competent and immune compromised ID8 and ID8 VEGF tumor-bearing mice demonstrated a decreased response to cisplatin therapy in ABX treated groups with an increase in overall tumor burden. RNAseq analysis showed enrichment of multiple cell proliferation and stem cell pathways, and stem cell genes SOX2, WNT and PAX2. The self-renewal of ABX treated tumor cells was also increased.Conclusion: Collectively, these studies indicate an intact microbiome provides a tumor suppressive microenvironment and enhances sensitivity to cisplatin.


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