Guinan, J. | bioRxiv Science

bioRxiv2018

Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids promote gastrointestinal colonization of Candida albicans

Candida albicans is the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemic C. albicans infections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to prevent C. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization of C. albicans. Our results indicate that cefoperazone-treated mice susceptible to C. albicans infection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, using in vivo concentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development of C. albicans in vitro. Collectively, results from this study demonstrate that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization of C. albicans.

microbiology↗

bioRxiv2018

Auditory attention reduced ear-canal noise in humans, but not through medial olivocochlear efferent inhibition: Implications for measuring otoacoustic emissions during behavioral task performance

Otoacoustic emissions (OAEs) are often measured to non-invasively determine activation of medial olivocochlear (MOC) efferents in humans. Usually these experiments assume that ear-canal noise remains constant. However, changes in ear-canal noise have been reported in some behavioral experiments. We studied the variability of ear-canal noise in eight subjects who performed a two-interval-forced-choice (2IFC) sound-level-discrimination task on monaural tone pips in masking noise. Ear-canal noise was recorded directly from the unstimulated ear opposite the task ear. Recordings were also done with similar sounds presented, but no task done. In task trials, ear-canal noise was reduced at the time the subject did the discrimination, relative to the noise level earlier in the trial. In two subjects, there was a decrease in ear-canal noise, primarily at 1-2 kHz, with a time course similar to that expected from inhibition by MOC activity elicited by the task-ear masker noise. These were the only subjects with spontaneous OAEs (SOAEs). We hypothesize that the SOAEs were inhibited by MOC activity elicited by the task-ear masker. Based on the standard rationale in OAE experiments that large bursts of noise are artifacts due to subject movement, noise bursts above a sound-level criterion were removed. As the criterion was lowered and more high-and moderate-level noise bursts were removed, the reduction in noise level from the beginning of the trial to the time of the 2IFC discrimination became less. This pattern is opposite that expected from MOC inhibition (which is greater on lower-level sounds), but can be explained by the hypothesis that subjects move less and create fewer bursts of noise when they concentrate on doing the task. In contrast, for the six subjects with no SOAEs, in no-task trials the noise level was little changed throughout the trial. Our results show that measurements of MOC effects on OAEs must measure and account for changes in ear-canal noise, especially in behavioral experiments. The results also provide a novel way of showing the time course of the buildup of attention in ear-canal noise during a 2IFC task.

neuroscience↗