Effects of different amoxicillin treatment durations on microbiome diversity and composition in the gut

Abstract

Antibiotics seize an effect on bacterial composition and diversity and have been demonstrated to induce disruptions on gut microbiomes. This may have implications for human health and wellbeing, and an increasing number of studies suggest a link between the gut microbiome and several diseases. Hence, reducing antibiotic treatments may be beneficial for human health status. Further, antimicrobial resistance (AMR) is an increasing global problem that can be counteracted by limiting the usage of antibiotics. Longer antibiotic treatments have been demonstrated to increase the development of AMR. Therefore, shortening of antibiotic treatment durations, provided it is safe for patients, may be one measure to reduce AMR. In this study, the objective was to investigate effects of standard and reduced antibiotic treatment lengths on gut microbiomes using a murine model. Changes in the murine gut microbiome was assessed after using three different treatment durations of amoxicillin (3, 7 or 14 days) as well as a control group not receiving amoxicillin. Fecal samples were collected before and during the whole experiment, until three weeks past end of treatment. These were further subject for 16S rRNA Illumina MiSeq sequencing. Our results demonstrated significant changes in bacterial diversity, richness and evenness during amoxicillin treatment, followed by a reversion in terms of alpha-diversity and abundance of major phyla, after end of treatment. However, a longer restitution time was indicated for mice receiving amoxicillin for 14 days, and phylum Patescibacteria did not fully recover. In addition, an effect on the composition of Firmicutes was indicated to last for at least three weeks in mice treated with amoxicillin for 14 days. Despite an apparently reversion to a close to original state in overall bacterial diversity and richness, the results suggested more durable changes in lower taxonomical levels. We detected several families, genera and ASVs with significantly altered abundance three weeks after exposure to amoxicillin, as well as bacterial taxa that appeared significantly affected by amoxicillin treatment length. This may strengthen the argument for shorter antibiotic treatment regimens to both limit the emergence of antibiotic resistance and risk of gut microbiome disturbance.

Antibiotic Exposure Concurrently with Anti-PD1 Blockade Therapy Reduces Overall Survival in Patients with Child–Pugh Class A Advanced Hepatocellular Carcinoma

“…Our findings show a significant association between antibiotic use and reduced overall survival in patients with HCC and Child–Pugh class A cirrhosis undergoing ICI treatment. This finding aligns with growing evidence suggesting the gut microbiota, which can be influenced by Ceftriaxone [ 30 ], Ciprofloxacin [ 31 ], Pipracillin/tazobactam [ 32 ], Meropenem [ 33 ], Augmentin [ 34 ], and Moxifloxacin [ 35 ] antibiotics used in our cohort, as indicated in Table 2 , significantly play a crucial role in regulating response to ICIs [ 23 , 36 ]. Furthermore, no differences in the overall survival in patients with HCC and Child–Pugh class B cirrhosis undergoing ICI treatment.…”

“…Augmentin [34], and Moxifloxacin [35] antibiotics used in our cohort, as indicated in Table 2, significantly play a crucial role in regulating response to ICIs [23,36]. Furthermore, no differences in the overall survival in patients with HCC and Child-Pugh class B cirrhosis undergoing ICI treatment.…”

Characterization of upper airway microbiome across severity of COVID-19 during hospitalization and treatment

“…Our study corroborates with these findings, as there was no difference alpha diversity between severe/critical and asymptomatic COVID-19 when confounding by use of antimicrobial was removed. These results are consistent with animal and human non–COVID-19 studies that generally demonstrated that antimicrobial use reduces bacterial alpha diversity ( Huang et al., 2022 ; Kwon et al., 2022 ; Lekang et al., 2022 ). However, exclusion or statistical adjustment of samples for antimicrobial use was often not done or reported in COVID-19–related microbiome studies ( Ma et al., 2021 ; Merenstein et al., 2021 ; Rueca et al., 2021 ; Ventero et al., 2021 ; Chen et al., 2022 ; Gauthier et al., 2022 ).…”

Marginal notes, November 2022. From crisis to crisis

“…So-called broad-spectrum antimicrobials are known to cause a loss of taxonomic richness and diversity during intake, followed by a long time to restore bacterial homeostasis. A study of mouse microbiota after amoxicillin treatment for 0, 3, 7 or 14 days shows this to be the case, with the greatest impact in the 14-day treatment group [4]. Interestingly, this study demonstrated that the shortest treatment (3 days) produced longer lasting microbiome effects in some bacterial taxa for several weeks.…”