Monedeiro, F. | bioRxiv Science

bioRxiv2026

Enhanced environmental complexity worsens experimental colitis and dysregulates microbiota-gut-brain axis signalling in female mice

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by colonic inflammation and bloody diarrhoea. Accumulating evidence suggests that UC not only affects the intestinal tract, but also distant organs including the brain. Environmental factors are key determinants of the disease course, yet the impact and potential disease modifying effects of living environment complexity on microbiota-gut-brain axis signalling during colitis remain unclear. To address this gap, we investigated how enhanced environmental complexity (EC) affects the disease course and gut-brain axis signalling during experimental colitis in mice. Our results show that EC exacerbates dextran sulphate sodium (DSS)-induced colitis in female mice, but not in male mice, as evidenced by greater weight loss and higher disease activity. Immune cell profiling across the gut-brain axis reveals strong effects of DSS treatment on colonic, circulating and brain immune cell populations and a restriction of central nervous system (CNS) T cell infiltration due to EC. In addition, female EC/DSS mice have higher circulating corticosterone levels than controls indicating chronic stress. Metabolomics across the gut-brain axis revealed that EC exacerbates colitis-induced metabolite perturbations in plasma, brain tissue, brain interstitial and cerebrospinal fluid. Notably, microbiota-derived metabolites, including deoxycholic acid and trimethylamine-N-oxide (TMAO), are increased in EC/DSS mice, concordant with EC-associated microbiome changes and anxiety-like behaviour. Overall, this study indicates that EC worsens experimental colitis in female mice and directs microbiota-gut-brain axis signalling during colitis towards a less favourable state. From a translational perspective, this study highlights the importance of environmental factors for a sex-specific disease course of UC and associated neurobehavioral comorbidities. HighlightsO_LIEnhanced environmental complexity (EC) exacerbates experimental colitis C_LIO_LIColitis and EC have compartment-specific effects on immune cells C_LIO_LIEC augments colitis-induced metabolic shifts in plasma, brain and CSF C_LIO_LIMicrobiota-derived metabolites are important players for the effects of EC C_LI

neuroscience↗

bioRxiv2024

Urine microbiome changes during and after radiotherapy for prostate cancer

BackgroundThe urinary microbiome may play a new important role in the development of complications, but still, there is no information about their changes during and after radiotherapy (RT). This study aimed to use the matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) technique to identify the microbiome and assess its changes in urine samples of 88 patients irradiated for prostate cancer. Material and methodsBlood for biochemical analysis and urine samples for MALDI were collected at various time points before gold fiducial implantation (t1) at the beginning (t2) and end of radiotherapy (t3); during follow-up, 1 (t4), 4 (t5), 7 (t6) months after the end of treatment. ResultsWe identified 1801 different microbial isolates, in 89% (470/528) samples revealed the presence of at least one microbial species among which 79% (373/470) were polymicrobial. Species level: 136 G+, 29 G-, 2 Candida have been noted. The far most abundant group of the identified microorganisms was Staphylococcus members -51.6% of all isolates followed by Micrococcus (9.1%), Enterococcus (7.6%), Kocuria (5.6%), Corynebacterium (5.4%), and Streptococcus (2.2%). A lower variety of microorganisms incident was observed at the end of RT. The total number of species (TNS) was 50 at t1, increased up to 61 at t2, and then fell to the initial value of 52 at t3. The increase in biodiversity was noted after radiotherapy t4-68, t5-86, and t6-75 (p<0.05). Changes in the biodiversity of the urinary microbiota were also reflected in the differences in the total number of isolates (TNI) - 261, 281, and 273 for time points t1-t3 compared to the 292, 362, and 332 for time points t4-t6 as well as in the total number of detected genera (TNG) - 25, 29, 23 (t1-t3) and 28, 38, 31 (t4-t6). Actinomyces, Corynebacterium, Staphylococcus, Streptococcus, demonstrated significant correlation with the RT stages. Concerning individual species, only K. rhizophila abundance significantly increased with time (p=0.045). Bacteria incidence was strongly correlated with glucose levels in urine. The same correlation was observed for glucose levels in blood, but in a weak manner. Staphylococcus presence was related to higher tPSA. ConclusionRT for prostate cancer induces a dynamic response in the urinary microbiome, characterized by an initial reduction in diversity post-RT followed by a subsequent increase. Our findings highlight the significant influence of glucose levels in both urine and blood on the urinary microbiota. These insights contribute to the evolving understanding of the interplay between RT, the urinary microbiome, and patient health, paving the way for more targeted interventions and personalized approaches in prostate cancer treatment.

microbiology↗