Do antibiotics cause mitochondrial and immune cell dysfunction? A literature review

Miller, Muska; Singer, Mervyn

doi:10.1093/jac/dkac025

Cited by 18 publications

(11 citation statements)

References 223 publications

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“…Moreover, it was recently shown that chitin metabolism pathways are regulated by the microbiome, which is consistent with the gene ontology analysis of the antibiotic constant condition ( Domin et al, 2023 ). One of the upregulated transcripts in the antibiotic constant treatment was Cytochrome C, which is central for mitochondrial function for ATP synthesis and apoptosis, suggesting that antibiotics can target metabolic processes within the host cells ( Miller & Singer, 2022 ). While antibiotic off target effects on Cytochrome C has not been described in N. vectensis, exposure of Oryzias latipes and Danio rerio to erythromycin, a macrolide, showed downregulation of Cytochrome C, as well as a variety of other metabolism-related genes, reduced locomotion, and energy metabolism ( Li & Zhang, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Exposure of Branchiostoma belcheri , a cephalochordate, to antibiotics resulted in sublethal effects including immunosuppression and a reduction in eicosanoids ( Yuan et al, 2015 ). Moreover, antibiotics can directly affect the function and efficacy of mitochondria within the host cells ( Kovalakova et al, 2020 ; Miller & Singer, 2022 ; Singh, Sripada & Singh, 2014 ). While antibiotics can reduce and potentially kill bacteria in a host, the direct effects of these compounds on the host are understudied ( Baralla et al, 2021 ; Bojarski, Kot & Witeska, 2020 ; Yang, Song & Lim, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Antibiotics alter development and gene expression in the model cnidarian Nematostella vectensis

Krueger,

Phippen,

Reitzel

2024

PeerJ

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Background Antibiotics are commonly used for controlling microbial growth in diseased organisms. However, antibiotic treatments during early developmental stages can have negative impacts on development and physiology that could offset the positive effects of reducing or eliminating pathogens. Similarly, antibiotics can shift the microbial community due to differential effectiveness on resistant and susceptible bacteria. Though antibiotic application does not typically result in mortality of marine invertebrates, little is known about the developmental and transcriptional effects. These sublethal effects could reduce the fitness of the host organism and lead to negative changes after removal of the antibiotics. Here, we quantify the impact of antibiotic treatment on development, gene expression, and the culturable bacterial community of a model cnidarian, Nematostella vectensis. Methods Ampicillin, streptomycin, rifampicin, and neomycin were compared individually at two concentrations, 50 and 200 µg mL−1, and in combination at 50 µg mL−1 each, to assess their impact on N. vectensis. First, we determined the impact antibiotics have on larval development. Next Amplicon 16S rDNA gene sequencing was used to compare the culturable bacteria that persist after antibiotic treatment to determine how these treatments may differentially select against the native microbiome. Lastly, we determined how acute (3-day) and chronic (8-day) antibiotic treatments impact gene expression of adult anemones. Results Under most exposures, the time of larval settlement extended as the concentration of antibiotics increased and had the longest delay of 3 days in the combination treatment. Culturable bacteria persisted through a majority of exposures where we identified 359 amplicon sequence variants (ASVs). The largest proportion of bacteria belonged to Gammaproteobacteria, and the most common ASVs were identified as Microbacterium and Vibrio. The acute antibiotic exposure resulted in differential expression of genes related to epigenetic mechanisms and neural processes, while constant application resulted in upregulation of chaperones and downregulation of mitochondrial genes when compared to controls. Gene Ontology analyses identified overall depletion of terms related to development and metabolism in both antibiotic treatments. Discussion Antibiotics resulted in a significant increase to settlement time of N. vectensis larvae. Culturable bacterial species after antibiotic treatments were taxonomically diverse. Additionally, the transcriptional effects of antibiotics, and after their removal result in significant differences in gene expression that may impact the physiology of the anemone, which may include removal of bacterial signaling on anemone gene expression. Our research suggests that impacts of antibiotics beyond the reduction of bacteria may be important to consider when they are applied to aquatic invertebrates including reef building corals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antibiotics alter development and gene expression in the model cnidarian Nematostella vectensis

Krueger,

Phippen,

Reitzel

2024

PeerJ

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“…So kommt es hier vermehrt zu einem Auftreten von bakteriellen Fehlbesiedelungen, was wiederum zu einer Begünstigung von Sekundärinfektionen führen kann [5]. Zudem wurde bereits ein möglicher Einfluss der Antibiotika auf die mitochondriale Funktion und damit auch auf das Immunsystem diskutiert [22]. Persistierende proinflammatorische Stimuli tragen konsekutiv zu einer progressiven immunsuppressiven Reaktion im Sinne eines aggravierten CARS bei, welches mit dem Zustand der Chronic Critical Illness (CCI) assoziiert wird.…”

Section: Lisowska Et Al Beschrieben In Einer Klinischen Studie Beispi...unclassified

Das Immunsystem des kritisch Kranken

Vogeler,

Schenz,

Müller

et al. 2024

Anästhesiol Intensivmed Notfallmed Schmerzther

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“…Common examples include catecholamines, vasopressin or its analogues, corticosteroids and insulin. The stress response and immune function are also modified by other routine interventions, for example the use of immunomodulating sedative drugs [ 154 ] and a decrease in sympathetic activity due to the patient being asleep.…”

Section: Impact Of Hormonal Changes On Immune Cell Functionmentioning

confidence: 99%

The role of hormones in sepsis: an integrated overview with a focus on mitochondrial and immune cell dysfunction

et al. 2023

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Sepsis is a dysregulated host response to infection that results in life-threatening organ dysfunction. Virtually every body system can be affected by this syndrome to greater or lesser extents. Gene transcription and downstream pathways are either up- or downregulated, albeit with considerable fluctuation over the course of the patient’s illness. This multi-system complexity contributes to a pathophysiology that remains to be fully elucidated. Consequentially, little progress has been made to date in developing new outcome-improving therapeutics. Endocrine alterations are well characterised in sepsis with variations in circulating blood levels and/or receptor resistance. However, little attention has been paid to an integrated view of how these hormonal changes impact upon the development of organ dysfunction and recovery. Here, we present a narrative review describing the impact of the altered endocrine system on mitochondrial dysfunction and immune suppression, two interlinked and key aspects of sepsis pathophysiology.

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Do antibiotics cause mitochondrial and immune cell dysfunction? A literature review

Cited by 18 publications

References 223 publications

Antibiotics alter development and gene expression in the model cnidarian Nematostella vectensis

Antibiotics alter development and gene expression in the model cnidarian Nematostella vectensis

Das Immunsystem des kritisch Kranken

The role of hormones in sepsis: an integrated overview with a focus on mitochondrial and immune cell dysfunction

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