Biology subjects

Bassis, C.

Publications and source records attributed to Bassis, C..

4 recordsLinked to original sources

bioRxiv2021

Gut microbiome features are associated with sepsis onset and outcomes

BackgroundEpidemiologic studies have linked antibiotic exposure to subsequent sepsis, suggesting that microbiome disruption may be in the causal pathway and an independent risk factor. This study tests whether variation in the gut microbiota associates with risk of sepsis onset and its outcomes. MethodsUsing a validated surveillance definition, patients with an archived rectal swab from intensive care and hematology units were screened for sepsis. After confirmation by chart review, cases were matched to controls in a 1:2 ratio based on age, gender, and collection date. Relative taxon abundance was measured by sequence analysis of 16S rRNA gene amplicons; total bacterial abundance was measured by qPCR of the 23S rRNA gene. Conditional logistic regression identified clinical and microbiota variables associated with sepsis. ResultsThere were 103 sepsis cases matched to 206 controls. In a final model adjusting for exposure to broad-spectrum antibiotics and indwelling vascular catheters, high relative abundance (RA) of Enterococcus (Odds Ratio (OR) 1.36 per 10% increase, P=.016) and high total bacterial abundance (OR 1.50 per 10-fold increase in 23S copies/L, P =.001) were independently associated with sepsis. Decreased RA of butyrate-producing bacteria also independently associated with sepsis (OR 1.20 for 10% decrease in RA, P =.041), and mortality in unadjusted analysis (OR=1.47 for 10% decrease in RA, P=.034). ConclusionsThis study indicates that the microbiota is altered at sepsis onset. The decreased RA of butyrate-producing bacteria in sepsis also associates with mortality, suggesting a therapeutic role for prebiotics and probiotics in the prevention and treatment of sepsis. ImportanceEarly detection of patients at risk for sepsis could enable interventions to prevent or rapidly treat this life-threatening condition. Prior antibiotic treatment is associated with sepsis, suggesting that disruption of the bacterial population in the gut (the intestinal microbiome) could be an important step leading to disease. To investigate this theory, we matched hospitalized patients with and without sepsis and characterized the patients microbiomes close to or at onset of sepsis. We found that several microbiome alterations, including having more total bacteria in the gut was associated with onset, regardless of prior antibiotic treatment. This signature of microbiome disruption brings us closer to identifying the biological causes of sepsis and could be used to develop new diagnostic tests to identify patients at risk of sepsis.

microbiology↗

bioRxiv2020

A plasmid locus associated with Klebsiella clinical infections encodes a microbiome-dependent gut fitness factor

Introductory paragraphGut colonization by the pathogen Klebsiella pneumoniae (Kp) is consistently associated with subsequent Kp disease1-5, and patients are predominantly infected with their colonizing strain1,2. However, colonizing strains likely vary in their potential to cause infection. We previously identified the plasmid-encoded tellurium resistance (ter) operon as highly associated with infection when compared to asymptomatic colonization in hospitalized patients1. The ter operon bestows resistance to the toxic compound tellurite oxide (TeO3-2), but this is unlikely to be its physiological function, as tellurium and TeO3-2 are exceedingly rare. Here we show that terC is necessary and terZABCDEF is sufficient for phenotypic TeO3-2 resistance. Next, we demonstrate that ter is encoded on a diverse group of plasmids without known plasmid-encoded virulence genes, suggesting an independent role in infection. Finally, our studies indicate that ter is a gut fitness factor, and its fitness advantage is conferred only when specific gut microbiota constituents are present. Collectively, these data reveal the Kp ter operon that is highly associated with human infection likely acts early in pathogenesis as a horizontally-transferrable fitness factor promoting robust gut colonization in the presence of the indigenous microbiota.

microbiology↗

bioRxiv2019

The rodent vaginal microbiome across the estrous cycle and the effect of genital nerve electrical stimulation

Treatment options are limited for the approximately 40% of postmenopausal women worldwide who suffer from female sexual dysfunction (FSD). Neural stimulation has shown potential as a treatment for genital arousal FSD, however the mechanisms for its improvement are unknown. One potential cause of some cases of genital arousal FSD are changes to the composition of the vaginal microbiota, which is associated with vulvovaginal atrophy. The primary hypothesis of this study was that neural stimulation may induce healthy changes in the vaginal microbiome, thereby improving genital arousal FSD symptoms. In this study we used healthy rats, which are a common animal model for sexual function, however the rat vaginal microbiome is understudied. Thus this study also sought to examine the composition of the rat vaginal microbiota. Treatment rats (n=5) received 30 minutes of cutaneous electrical stimulation targeting the genital branch of the pudendal nerve, and Control animals (n=4) had 30-minute sessions without stimulation. Vaginal lavage samples were taken during a 14-day baseline period including multiple estrous periods and after twice-weekly 30-minute sessions across a six-week trial period. Analysis of 16S rRNA gene sequences was used to characterize the rat vaginal microbiota in baseline samples and determine the effect of stimulation. We found that the rat vaginal microbiota is dominated by Proteobacteria, Firmicutes, and Actinobacteria, which changed in relative abundance during the estrous cycle and in relationship to each other. While the overall stimulation effects were unclear in these healthy rats, some Treatment animals had less alteration in microbiota composition between sequential samples than Control animals, suggesting that stimulation may help stabilize the vaginal microbiome. Future studies may consider additional physiological parameters, in addition to the microbiome composition, to further examine vaginal health and the effects of stimulation.

microbiology↗

bioRxiv2019

Evaluation of Bacteria Detected in Both Urine and Open Wounds in Nursing Facility Residents

Nursing home residents are at a greater risk of developing pressure injuries that develop into an open wound. Open wounds can be colonized with bacteria from multiple sources. Emerging evidence suggests the specific composition of the open wound microbial community can result in delayed wound healing and increased infection risk. Understanding the factors that influence microbial colonization of open wounds, can lead to the prevention of infections. The relationship between bacteria found in urine and that of open wounds, is currently unknown. Recent studies have shown that nursing home residents can harbor a urinary microbiota independent of symptoms and frequently experience urinary incontinence. To determine if the colonization of open wounds mirrors urinary colonization, we conducted a pilot study with nursing home residents, comparing bacteria present in open pressure injuries below the umbilicus and urine. To identify microbial species that were present in both urine and open wound at one timepoint, standard bacteriologic culture techniques followed by MALDI-TOF was used as well as16S rRNA-encoding gene amplicon sequencing. In this study we found that some bacteria detected in urine were also detected in open wounds in one individual at one timepoint, using both culture dependent and independent techniques. Bacterial species that were more often detected at both sites included Enterococcus faecalis, Proteus mirabilis, Escherichia coli, and Providencia stuartii. This pilot study provides evidence that urinary colonization can mirror open wound colonization. Further studies are needed to investigate if parallel colonization of these anatomical sites affect infection outcomes.

microbiology↗