Effects of Carboxymethylcellulose Artificial Tears on Ocular Surface Microbiome Diversity and Composition, A Randomized Controlled Trial.

Purpose: Carboxymethylcellulose is an artificial tear ingredient known to decrease gut microbiome diversity when ingested. This study examines the effect of carboxymethylcellulose on ocular surface microbiome diversity and composition. Methods: Healthy adult participants without significant ophthalmic disease or concurrent carboxymethylcellulose artificial tear use were allocated randomly to take carboxymethylcellulose or control polyethylene glycol artificial tears for seven days. Conjunctival swabs were collected before and after artificial tear treatment. This trial is registered at clinicaltrials.gov (NCT05292755). Primary outcomes included abundance of bacterial taxa and microbiome diversity as measured by the Chao-1 richness estimate, Shannon's phylogenetic diversity index, and UniFrac analysis. Secondary outcomes included Ocular Surface Disease Index scores and artificial tear compliance. Results: Of the 80 enrolled participants, 66 completed the trial. Neither intervention affected Chao-1 richness (analysis of variance [ANOVA], P = 0.231) or Shannon's diversity index (ANOVA, P = 0.224). Microbiome samples did not separate by time point (permutation multivariate analysis of variance [PERMANOVA], P = 0.223) or intervention group (PERMANOVA, P = 0.668). LEfSe taxonomic analysis revealed that carboxymethylcellulose depleted several taxa including Bacteroides and Lachnoclostridium, but enriched Enterobacteriaceae, Citrobacter, and Gordonia. Both interventions decreased OSDI scores (Wilcoxon signed rank test, P < 0.05), but there was no significant difference between interventions (Mann-Whitney U, P = 0.54). Conclusions: Carboxymethylcellulose artificial tears increased Actinobacteriota but decreased Bacteroides and Firmicutes bacteria. Carboxymethylcellulose artificial tears do not affect ocular surface microbiome diversity and are not significantly more effective than polyethylene glycol artificial tears for dry eye treatment. Translational Relevance: The 16S microbiome analysis has revealed small changes in the ocular surface microbiome associated with artificial tear use.

A randomized controlled trial to evaluate the effectiveness of a novel mouth rinse in patients with gingivitis.

BACKGROUND: This single-center, randomized controlled trial aimed to determine the effectiveness of a novel, biofilm-disrupting, mouth rinse that combines Cetylpyridinium chloride (CPC) and essential oils in preventing re-accumulation of supragingival plaque and supragingival microbiome in patients with gingivitis after dental prophylaxis. METHODS: One hundred eighteen participants were randomly assigned in a 1:1 ratio to receive twice-daily test mouth rinse (59) or carrier rinse control (59) for 12 weeks after dental prophylaxis. RESULTS: In a per-protocol analysis that included patients who completed the intervention, the treatment group (39) had significantly lower supragingival plaque scores at 6 and 12 weeks compared to the control group (41; p = 0.022). Both groups showed similar improvement in gingivitis score, but neither group had improvement in bleeding score or probing depth. Thirty-eight (29%) patients did not complete the study due to loss of follow-up (17) or early discontinuation of the assigned intervention (21). Microbiome sequencing showed that the treatment rinse significantly depleted abundant and prevalent members of the supragingival plaque microbiome consortium. CONCLUSIONS: Among patients with gingivitis, the novel mouth rinse significantly reduced re-accumulation of supragingival plaque following dental prophylaxis by depleting supragingival plaque microbiome. However, long-term adherence to the rinse may be limited by adverse effects ( ClinicalTrials.gov number, NCT03154021).

Linkage of resistance-associated substitutions in GT1 sofosbuvir + NS5A inhibitor failures treated with glecaprevir/pibrentasvir.

BACKGROUND & AIMS: Retreatment with glecaprevir/pibrentasvir (G/P) resulted in a rate of sustained virologic response 12 weeks after treatment completion (SVR12) of >90% in HCV genotype 1 (GT1) patients who previously failed a regimen of sofosbuvir plus an NS5A inhibitor (NS5Ai). This study investigated the prevalence and impact of baseline NS3 and NS5A resistance-associated substitutions (RASs) on the efficacy of G/P in prior GT1 sofosbuvir+NS5Ai failures and the persistence of treatment-emergent RASs. METHODS: Longitudinal samples from 177 patients enrolled in a phase IIIb, randomized pragmatic clinical trial were analyzed. Patients without cirrhosis were randomized to 12 or 16 weeks of G/P, and patients with compensated cirrhosis were randomized to G/P and ribavirin for 12 weeks or G/P for 16 weeks. Linkage of RAS was identified using Primer-ID next-generation sequencing at a 15% cut-off. RESULTS: Of 177 patients, 169 (95.5%) were PI-naïve. All 33 GT1b-infected patients achieved SVR12. In GT1a-infected patients, baseline NS5A RASs were prevalent (74.5%, 105/141) but NS3 RASs were uncommon. Baseline NS3 RASs had no impact on G/P efficacy and patients with baseline NS5A RASs showed a numerically but not statistically significantly lower SVR12 rate compared to those without NS5A RASs (89% vs. 97%). SVR12 was achieved in 34 of 35 (97%) patients without NS5A baseline substitution, and 53 of 57 (93%), 35 of 40 (88%), 5 of 8 (63%) with single, double-linked, and triple-linked NS5A substitutions, respectively. Among 13 patients with virologic failure, 4 acquired treatment-emergent NS3 RASs and 10 acquired NS5A RASs. CONCLUSION: Baseline NS5A RASs were highly prevalent. The presence of an increasing number of linked NS5A RASs in GT1a showed a trend in decreasing SVR12 rates, although no specific NS5A RASs or their linkage pattern were associated with lower SVR12 rates. LAY SUMMARY: Direct-acting antivirals have revolutionized the treatment of chronic hepatitis C infection, but treatment failure occurs in some patients. Retreatment of patients who previously failed a regimen consisting of sofosbuvir and an NS5A inhibitor with a regimen of glecaprevir and pibrentasvir (G/P) is >90% effective. Herein, we analyzed samples from these patients and showed that retreatment efficacy with G/P is lower in patients with double- or triple-linked NS5A resistance mutations than in patients with single or no NS5A resistance mutations. CLINICAL TRIAL NUMBER: NCT03092375.

Deletion of a conserved transcript PG_RS02100 expressed during logarithmic growth in Porphyromonas gingivalis results in hyperpigmentation and increased tolerance to oxidative stress.

The oral obligate anaerobe Porphyromonas gingivalis possesses a small conserved transcript PG_RS02100 of unknown function we previously identified using small RNA-seq analysis as expressed during logarithmic growth. In this study, we sought to determine if PG_RS02100 plays a role in P. gingivalis growth or stress response. We show that a PG_RS02100 deletion mutant's (W83Δ514) ability to grow under anaerobic conditions was no different than wildtype (W83), but it was better able to survive hydrogen peroxide exposure when cultured under heme limiting growth conditions, and was more aerotolerant when plated on enriched whole blood agar and exposed to atmospheric oxygen. Together, these results indicate that PG_RS02100 plays a role in surviving oxidative stress in actively growing P. gingivalis and that P. gingivalis' response to exogenous hydrogen peroxide stress is linked to heme availability. Relative qRT-PCR expression analysis of oxyR, trx-1, tpx, sodB, ahpC, dinF, cydB, and frd, in W83Δ514 and W83 in response to 1 h exogenous dioxygen or hydrogen peroxide exposure, when cultured with varying heme availability, support our phenotypic evidence that W83Δ514 has a more highly primed defense system against exogenous peroxide, dioxygen, and heme generated ROS. Interestingly, W83Δ514 turned black faster than W83 when cultured on whole blood agar, suggesting it was able to accumulate heme more rapidly. The mechanism of increased heme acquisition observed in W83Δ514 is not yet known. However, it is clear that PG_RS02100 is involved in modulating the P. gingivalis cell surface in a manner related to survival, particularly against oxidative stress.

Genome Sequence of Porphyromonas gingivalis Strain A7A1-28.

Porphyromonas gingivalis is an oral opportunistic pathogen. Sequenced P. gingivalis laboratory strains display limited diversity in antigens that modulate host responses. Here, we present the genome sequence of A7A1-28, a strain possessing atypical fimbrillin and capsule types, with a single contig of 2,249,024 bp and a G+C content of 48.58%.

Genome Sequence of Porphyromonas gingivalis Strain 381.

Porphyromonas gingivalis is associated with both oral and systemic diseases. Strain-specific P. gingivalis invasion phenotypes do not reliably predict disease presentation during in vivo studies. Here, we present the genome sequence of 381, a common laboratory strain, with a single contig of 2,378,872 bp and a G+C content of 48.36%.

Genome Sequence of Porphyromonas gingivalis Strain AJW4.

Porphyromonas gingivalis is associated with oral and systemic diseases. Strain-specific P. gingivalis invasion phenotypes have been correlated with disease presentation in infected laboratory animals. Here, we present the genome sequence of AJW4, a minimally invasive strain, with a single contig of 2,372,492 bp and a G+C content of 48.27%.

Genome Sequence of Porphyromonas gingivalis Strain A7436.

Porphyromonas gingivalis is strongly associated with periodontitis. P. gingivalis strain trafficking and tissue homing differ widely, even among presumptive closely related strains, such as W83 and A7436. Here, we present the genome sequence of A7436 with a single contig of 2,367,029 bp and a G+C content of 48.33%.