Gut microbiota analyses of cutaneous T-cell lymphoma patients undergoing narrowband ultraviolet B therapy reveal alterations associated with disease treatment.

Recent studies have shown a close relationship between cutaneous T-cell lymphoma (CTCL) and its microbiome. CTCL disease progression is associated with gut dysbiosis and alterations in bacterial taxa parallel those observed in immunologically similar atopic dermatitis. Moreover, the microbial profile of lesional skin may predict response to narrowband ultraviolet B (nbUVB), a common skin-directed therapy. However, the relationship between the gut microbiome, an immunologically vital niche, and nbUVB remains unexplored in CTCL. Herein, we performed 16S rRNA sequencing and PICRUSt2 predictive metagenomics on DNA extracted from stool swabs of 13 CTCL patients treated with nbUVB, 8 non-treated patients, and 13 healthy controls. Disease response was assessed with modified Severity Weighted Assessment Tool (mSWAT); of nbUVB-treated patients, 6 improved (decreased mSWAT), 2 remained stable, and 5 worsened (increased mSWAT). Protective commensal bacteria including Lactobacillaceae and Erysipelatoclostridiaceae were significantly less abundant in CTCL patients compared to controls. With treatment, the CTCL gut microbiome exhibited decreased phylogenetic diversity and lower relative abundance of pro-inflammatory Sutterellaceae. Sutterellaceae was also significantly more abundant in patients who worsened, and Eggerthellaceae and Erysipelotrichaceae trended higher in patients who improved. Finally, PICRUSt2 functional predictions based on shifts in abundance of bacterial sequences repeatedly identified alterations in inositol degradation, which plays a key role in host immunomodulation, including inositol phospholipid signaling relevant to T-cell survival and proliferation. Our results bolster the paradigm of gut dysbiosis in CTCL and its functional implications in disease pathogenesis, and further delineate bacterial taxa associated with nbUVB response and with nbUVB treatment itself.

Time course of microglia activation and brain and blood cytokine/chemokine levels following chronic ethanol exposure and protracted withdrawal in rats.

Alcohol produces complex effects on the immune system. Moderate alcohol use (1-2 drinks per day) has been shown to produce anti-inflammatory responses in human blood monocytes, whereas, the post mortem brains of severe alcoholics show increased immune gene expression and activated microglial markers. The present study was conducted to evaluate the time course of alcohol effects during exposure and after withdrawal, and to determine the relationship between microglial and cytokine responses in brain and blood. Forty-eight adult, male Wistar rats were exposed to chronic ethanol vapors, or air control, for 5 weeks. Following ethanol/air exposure blood and brains were collected at three time points: 1) while intoxicated, following 35 days of air/vapor exposure; 2) following 24 h of withdrawal from exposure, and 3) 28 days after withdrawal. One hemisphere of the brain was flash-frozen for cytokine analysis, and the other was fixed for immunohistochemical analysis. The ionized calcium-binding adapter molecule 1 (Iba-1) was used to evaluate microglia activation at the three time points, and rat cytokine/chemokine Magnetic Bead Panels (Millipore) were used to analyze frontal cortex tissue lysate and serum. Ethanol induced a significant increase in Iba-1 that peaked at day 35, remained significant after 1 day of withdrawal, and was elevated at day 28 in frontal cortex, amygdala, and substantia nigra. Ethanol exposure was associated with a transient reduction of the serum level of the major pro- and anti-inflammatory cytokines and chemokines and a transient increase of effectors of sterile inflammation. Little or no changes in these molecules were seen in the frontal cortex except for HMG1 and fractalkine that were reduced and elevated, respectively, at day 28 following withdrawal. These data show that ethanol exposure produces robust microglial activation; however, measures of inflammation in the blood differ from those in the brain over a protracted time course.