Host gut resistome in Gulf War chronic multisymptom illness correlates with persistent inflammation

Bose, Dipro; Chatterjee, S.; Older, Ethan A.; Seth, Ratanesh; Janulewicz, Patricia; Saha, Punnag; Mondal, Ayan; Carlson, Jeffrey M.; Decho, Alan W.; Sullivan, Kimberly; Klimas, Nancy G.; Lasley, Stephen M.; Li, Jie; Chatterjee, Saurabh

doi:10.1038/s42003-022-03494-7

Cited by 6 publications

(6 citation statements)

References 94 publications

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“…Moreover, diseased hosts may be associated with a distinct but non-disease-specific resistome. Host inflammation and oxidative stress may promote phage lysogeny, increase horizontal gene transfer, and indirectly select for disease-associated bacteria rich in ARGs [ 19 , 25 – 27 ]. Currently, it is not known whether there is a consistent link between host disease and an expanded resistome.…”

Section: Introductionmentioning

confidence: 99%

Resistome expansion in disease-associated human gut microbiomes

Fredriksen,

de Warle,

van Baarlen

et al. 2023

Microbiome

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Background The resistome, the collection of antibiotic resistance genes (ARGs) in a microbiome, is increasingly recognised as relevant to the development of clinically relevant antibiotic resistance. Many metagenomic studies have reported resistome differences between groups, often in connection with disease and/or antibiotic treatment. However, the consistency of resistome associations with antibiotic- and non-antibiotic–treated diseases has not been established. In this study, we re-analysed human gut microbiome data from 26 case-control studies to assess the link between disease and the resistome. Results The human gut resistome is highly variable between individuals both within and between studies, but may also vary significantly between case and control groups even in the absence of large taxonomic differences. We found that for diseases commonly treated with antibiotics, namely cystic fibrosis and diarrhoea, patient microbiomes had significantly elevated ARG abundances compared to controls. Disease-associated resistome expansion was found even when ARG abundance was high in controls, suggesting ongoing and additive ARG acquisition in disease-associated strains. We also found a trend for increased ARG abundance in cases from some studies on diseases that are not treated with antibiotics, such as colorectal cancer. Conclusions Diseases commonly treated with antibiotics are associated with expanded gut resistomes, suggesting that historical exposure to antibiotics has exerted considerable selective pressure for ARG acquisition in disease-associated strains.

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Section: Introductionmentioning

confidence: 99%

Resistome expansion in disease-associated human gut microbiomes

Fredriksen,

de Warle,

van Baarlen

et al. 2023

Microbiome

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“…However, apart from pathological conditions, environmental exposure also greatly influences the host microbiome. Over the past few years, our group has extensively shown that environmental factors such as exposure to the cyanotoxin microcystin-LR (MC-LR) [35,36] and pesticides such as permethrin [63][64][65][66][67] also cause marked alteration in the host's gut microbiome composition, resulting in numerous adverse effects on the host's overall pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Subchronic Oral Cylindrospermopsin Exposure Alters the Host Gut Microbiome and Is Associated with Progressive Hepatic Inflammation, Stellate Cell Activation, and Mild Fibrosis in a Preclinical Study

Saha

Upright

Bose

et al. 2022

Toxins

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Epidemiological studies have reported a strong association between liver injury and incidences of hepatocellular carcinoma in sections of humans globally. Several preclinical studies have shown a strong link between cyanotoxin exposure and the development of nonalcoholic steatohepatitis, a precursor of hepatocellular carcinoma. Among the emerging threats from cyanotoxins, new evidence shows cylindrospermopsin release in freshwater lakes. A known hepatotoxin in higher concentrations, we examined the possible role of cylindrospermopsin in causing host gut dysbiosis and its association with liver pathology in a mouse model of toxico-pharmacokinetics and hepatic pathology. The results showed that oral exposure to cylindrospermopsin caused decreased diversity of gut bacteria phyla accompanied by an increased abundance of Clostridioides difficile and decreased abundance of probiotic flora such as Roseburia, Akkermanssia, and Bacteroides thetaiotamicron, a signature most often associated with intestinal and hepatic pathology and underlying gastrointestinal disease. The altered gut dysbiosis was also associated with increased Claudin2 protein in the intestinal lumen, a marker of gut leaching and endotoxemia. The study of liver pathology showed marked liver inflammation, the release of damage-associated molecular patterns, and activation of toll-like receptors, a hallmark of consistent and progressive liver damage. Hepatic pathology was also linked to increased Kupffer cell activation and stellate cell activation, markers of progressive liver damage often linked to the development of liver fibrosis and carcinoma. In conclusion, the present study provides additional evidence of cylindrospermopsin-linked progressive liver pathology that may be very well-linked to gut dysbiosis, though definitive evidence involving this link needs to be studied further.

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“…FMT can be used for the exclusion of antibiotic-resistant intestinal pathogens through colonization resistance, including C. difficile [8], vancomycin-resistant Enterococcu s [9], carbapenemase-producing Enterobacteriaceae [10], and multidrug-resistant (MDR) infections [11], although some person-specific heterogeneity in response has been reported [10]. In addition to ARO exclusion, evidence linking FMT administration to a reduction in ARG carriage by gut commensals stems from intestinal microbiota cultures [12], animal models [13], as well as human trials, primarily with patients administered antibiotics because of their direct impact on resistome expansion [14]. A study by Bajaj et al examined the impact of FMT on the fecal resistomes in patients with cirrhosis [15], who are often exposed to high levels of antibiotics because of hospitalizations and for the treatment of urinary and respiratory infections [16].…”

Section: Beneficial Impacts Of Fmt Administration On the Resistome An...mentioning

confidence: 99%

Double-edged sword: impact of fecal microbiome transplants on the gut resistome

Hallowell¹,

Gao²,

Suez³

2022

Current Opinion in Gastroenterology

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Purpose of reviewFecal microbiome transplants (FMT) show promise in treating various diseases, such as Clostridioides difficile infections. FMT have also demonstrated the capacity to modulate the collection of antibiotic resistance genes (ARGs), termed the resistome, within the gut. The purpose of this review was to critically evaluate the literature regarding the interaction between FMT and the gut resistome and determine whether FMT could be used specifically to reduce ARG carriage in the gut. Recent findingsSeveral studies have demonstrated a decrease in ARG carriage post-FMT administration in various disease states, including recurrent C. difficile infection and after antibiotic usage. However, other studies have reported an expansion of the resistome following FMT. Most studies contained small patient cohorts regardless of the outcome and showed heterogeneity in responses. SummaryResearch on resistome modulation by FMT is preliminary, and human studies currently lack consensus regarding benefits and risks. From a safety perspective, screening donor samples for ARGs in addition to antibiotic-resistant organisms may be advisable. Additional studies on the mechanisms underlying heterogeneity between studies and individuals are required before FMT is considered an efficient approach for resistome amelioration.

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Host gut resistome in Gulf War chronic multisymptom illness correlates with persistent inflammation

Cited by 6 publications

References 94 publications

Resistome expansion in disease-associated human gut microbiomes

Resistome expansion in disease-associated human gut microbiomes

Subchronic Oral Cylindrospermopsin Exposure Alters the Host Gut Microbiome and Is Associated with Progressive Hepatic Inflammation, Stellate Cell Activation, and Mild Fibrosis in a Preclinical Study

Double-edged sword: impact of fecal microbiome transplants on the gut resistome

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