Systematic review: human gut dysbiosis induced by non‐antibiotic prescription medications

Bastard, Quentin Le; Al‐Ghalith, Gabriel A.; Grégoire, Matthieu; Chapelet, Guillaume; Javaudin, François; Dailly, Éric; Batard, Éric; Knights, Dan; Montassier, Emmanuel

doi:10.1111/apt.14451

Cited by 205 publications

(149 citation statements)

References 120 publications

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“…23 Bile acids regulate glucose homeostasis through the activation of nuclear receptors such as the pregnane X receptor, and mount antimicrobial defences via activation of the vitamin D receptor. 24 Statins have been found to influence the human gut microbiome, 25 and remodelling of murine gut microbiota resulted in increased risk of diabetes in mice via pregnane X receptor activation. 26 The clinical implication of gut dysbiosis associated with statins is uncertain as our study could not verify this mechanism.…”

Section: Figurementioning

confidence: 99%

A sequence symmetry analysis of the interrelationships between statins, diabetes and skin infections

Lareu

Dix

et al. 2019

Brit J Clinical Pharma

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Aims To determine statins' impact on skin infection risk in view of conflicting literature: that statins may reduce infection risk, but are also associated with diabetes mellitus, a risk factor for skin and soft tissue infections (SSTIs). Methods Sequence symmetry analysis was performed on prescription claims (2001–2011) from the Australian Department of Veterans' Affairs to determine the interrelationships between: (i) statins and SSTIs; (ii) statins and diabetes; and (iii) diabetes and SSTIs; as well as whether statins increased the risk of SSTIs, independent of diabetes status. Chi‐square tests were performed to detect differences in Index of Relative Socio‐economic Advantage and Disadvantage scores of patients within each interrelationship. Prescriptions for statins, antidiabetic medication, and antistaphylococcal antibiotics were evaluated using nonidentifiable client numbers, prescription dates filled, residential electorates, and pharmaceutical codes. Adjusted sequence ratio and confidence interval were calculated at intervals of 91, 182 and 365 days for sequence symmetry analysis studies. Results Statins were associated with: (i) significant SSTI risk (adjusted sequence ratio > 1; confidence interval >1), (ii) significant diabetes risk, and (iii) diabetic patients had increased risk of SSTIs. Diabetic and nondiabetic statin users had significantly increased risks of SSTIs, while the influence from socioeconomic status was not significant for each of the 3 relationships. Conclusions Statins are associated with increased risk of SSTIs via direct and indirect mechanisms, probably independent of diabetes or socioeconomic statuses. We believe that clinicians should be aware of the association between statins and SSTIs, and, where appropriate, monitor blood glucose levels of statin users.

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Section: Figurementioning

confidence: 99%

A sequence symmetry analysis of the interrelationships between statins, diabetes and skin infections

Lareu

Dix

et al. 2019

Brit J Clinical Pharma

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“…16s rRNA microbiome analysis of the bacterial community micro-dissected from the biofilm revealed that Gammaproteobacteria, a bacterial class associated with antibiotic induced dysbiosis, are in much lower abundance in the biofilm compared to adjoining areas. In a healthy gut, members of phylum Proteobacteria are normally maintained at very low levels but expand significantly in dysbiosis (Le Bastard et al, 2018; Rivera-Chavez et al, 2017). Increased abundance of class Gammaproteobacteria is seen in metabolic disorders (Larsen et al, 2010; Qin et al, 2012), obesity (Fei and Zhao, 2013; Sen et al, 2017), and inflammatory bowel disease (Gevers et al, 2014), all pathologies characterized by intestinal inflammation (Sen et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Spatial analysis of gut microbiome reveals a distinct ecological niche associated with the mucus layer

Duncan

Ewend

Vaishnava

2019

Preprint

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Colonic mucus bacterial communities are critical for determining disease pathology and promoting colonization resistance. Yet the key ecological properties of mucus resident communities that make them crucial for maintaining homeostatic microbiome function remain poorly defined. Using an approach that combines in situ hybridization, laser microdissection and 16s rRNA sequencing of spatially distinct regions of the mouse gut lumen, we discovered that the microbial community embedded in the mucus layer is structurally and compositionally distinct and drives stability of the gut microbiome. Structurally, the mucus residing microbial community had a higher density of bacteria than in the lumen and formed a biofilm-like structure whose integrity was dependent on Gram-positive commensals. Compositionally the dense mucus community excluded bacteria belonging to phylum Proteobacteria. Additionally, the dense bacterial community in the mucus was significantly more diverse and consisted of bacterial species that were unique to it. Upon antibiotic treatment, the species-rich and dense bacterial community in the mucus lost fewer Firmicutes and showed smaller bloom of Proteobacteria compared to the lumen. Taken together our work discloses a crucial role for the mucus layer in promoting stability of the gut microbiome in the perfused intestinal ecosystem by spatially entrenching unique and diverse bacterial species.

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“…The increasing prestige of the journal is reflected in the most recent increase in our impact factor (IF); during 2019, our 2‐year IF increased from 7.357 to 7.731 ranking AP&T in 11th place among 84 journals in gastroenterology and hepatology. The 10 papers published during 2018 that were the most highly cited during 2019 included such diverse topics as the epidemiology of Helicobacter pylori infection, the intestinal mirobiome and dysbiosis, biologic agents for IBD and evolving treatments for chronic viral hepatitis.…”

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confidence: 99%

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2019

Aliment Pharmacol Ther

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Systematic review: human gut dysbiosis induced by non‐antibiotic prescription medications

Abstract: SummaryBackground: Global prescription drug use has been increasing continuously for decades.

Cited by 205 publications

References 120 publications

A sequence symmetry analysis of the interrelationships between statins, diabetes and skin infections

A sequence symmetry analysis of the interrelationships between statins, diabetes and skin infections

Spatial analysis of gut microbiome reveals a distinct ecological niche associated with the mucus layer

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