Oral Competing Papers

The gut microbiota is emerging as a critical player in the physiology of organisms. Drosophila melanogaster is emerging as a powerful model for research into the gut microbiome and its impact on host physiology due to its conserved gut anatomy, major bacterial phyla, and tractable, well-defined gut microbiota. Furthermore, the short lifespan of D. melanogaster makes it more tractable for studying the relationship between the gut microbiota and aging. Although rodent models of the gut microbiota more closely resemble the complexity of the human microbiota, limitations such as expensive maintenance, complex care for generating germ-free animals, and ethical considerations make working with rodents difficult for gut microbiota studies. Unlike rodent models, the generation of germ-free flies is simple and easy to maintain, allowing for studies to determine the causality between the presence of gut microbiota and host physiology.  Dysbiosis, or the disruption of the normal flora of the microbiota, has been linked to a variety of diseases such as Alzheimer’s Disease, Parkinson’s Disease, among others. Furthermore, dysbiosis has been recognized as one of the hallmarks of aging, with aging-related changes in the gut microbiota composition being attributed to certain pathological outcomes in an organism’s aging process. As such, there has been an increasing interest in exploring the potential roles of the gut microbiota in modulating host physiology, such as through the gut-brain axis. In the present study, we hypothesized that aging-associated shifts in gut microbiota composition contribute to cognitive changes in Drosophila melanogaster. We conducted a learning and memory assay in young and old, male and female Drosophila melanogaster to determine their cognitive capacity. We profiled age- and sex-specific gut microbiota using both 16S rRNA and whole genome shotgun sequencing, uncovering compositional shifts that mirrored cognitive decline. Our data suggests that there is a 4-fold increase in Proteobacteria from young to old males and 9.85-fold increase from young to old females alongside a concomitant decrease in Firmicutes (5.5-fold decrease from young to old males and 11-fold decrease from young to old females). Furthermore, young males have more Proteobacteria (7.14-fold increase) and less Firmicutes (3.03-fold decrease) than young females. Future studies may explore causality by looking at cognitive changes in the context of a germ-free fly. These compositional shifts parallel cognitive decline, suggesting a potential microbial signature of aging. These findings position Drosophila as a scalable model to dissect the microbial contributors to age-related cognitive decline, offering a rapid preclinical platform to screen microbial or genetic interventions. 

Corresponding Author's Email Address: pmbmedina@post.upm.edu.ph

The present study investigated the effect of activating or inhibiting chemokine receptor type 4 (CXCR4) signaling in a murine macrophage cell line RAW264.7 cells and then evaluated using a mouse model BALB/c mice during Brucella abortus 544 infection. The uptake of Brucella and intracellular survival were determined at indicated time points and subsequently investigated the effect on the expression of mitogen-activated protein kinases (ERK1/2, JNK, p38α), generation of nitric oxide (NO) and induction of several cytokines in RAW264.7 cells. On the other hand, Brucella burden in the spleens was assessed as well as serum cytokine production was analyzed in BALB/c mice. The results showed that CXCR4 plays a role in the Brucella uptake accompanied by phosphorylation of ERK1/2, inhibition of NO production and expression of cytokines in vitro. Interestingly, AMD3100 treatment, a CXCR4 inhibitor, resulted in splenomegaly but reduced Brucella CFU in the spleens of mice with increased levels of MCP-1, TNF-ɑ and IL-12. The findings in this study contribute to a preliminary data on the potential contribution of CXCR4 signaling in the successful cell invasion and immune modulation during B. abortus infection. 

Corresponding Author's Email Address: abreyes4@up.edu.ph

Depression has been linked to gut health via the gut-brain axis, with changes in gut microbiota often associated with central nervous system disorders. The large intestine houses symbiotic bacteria essential for intestinal health, suggesting the potential of antidepressants and probiotics in regulating the gut-brain axis. This study investigated the effects of Lactobacillus rhamnosus GG (LGG), sertraline, and their concomitant use on the caecum and colon histomorphology of chronic unpredictable mild stress (CUMS)-induced Sprague-Dawley rats. The treatments include: Group 1 (CUMS with LGG), Group 2 (CUMS with sertraline), Group 3 (CUMS with combined treatments), Group 4 (CUMS with vehicle), and Group 5 (Non-stressed control with vehicle). Histological parameters involved colonic mucosal thickness, polymorphonuclear and goblet cell counts, and histological scores in both colon and caecum. Treatment Group 3 showed significantly greater colonic mucosal thickness (p = 0.005) and lower polymorphonuclear cell counts (p = 0.011) than Treatment Group 4, indicating a potential synergistic effect of LGG and sertraline in reducing colonic inflammation. Similar reductions in polymorphonuclear cells were observed in Treatment Group 2, suggesting that sertraline alone was effective in mitigating CUMS-induced inflammation, and LGG may not have added further benefits. Whereas, goblet cell counts showed no significant difference in both the caecum and the colon across treatment groups. Colonic histological scoring also revealed significant reductions in leukocyte infiltration severity (p = 0.012), epithelial erosion (p = 0.030), and mucosal ulceration (p = 0.028) in Treatment Group 3, indicating clear mucosal protection. In the caecum, significantly greater leukocyte infiltration extent (p = 0.011) and mucosal crypt loss (p = 0.022) in Treatment Group 1 compared to the non-stressed control suggest that LGG alone was insufficient to prevent CUMS-induced damage. Overall, LGG, sertraline, and their combination influence the colonic histomorphology of CUMS-induced rats, with combined treatment showing the most protective effects.

Corresponding Author's Email Address: rsvitor@up.edu.ph

Toluene is a widely abused addictive compound present in a variety of household and industrial products due to its accessibility and availability. A recent study showed that chronic exposure to toluene causes increased drug-seeking and general cognitive and social impairment (Asis et al, 2024). However, the effects of different treatment strategies on brain activity following toluene exposure has never been studied. This study investigated the effects of N-acetylcysteine and exercise as post exposure interventions in male and female Sprague-Dawley (SD) rats. Post-mortem analysis was performed on 72 biobanked brains from adolescent SD rats aged 4-6 weeks old previously exposed to either air or toluene for 12 days. During the abstinence period, animals received either NAC treatment or had access on voluntary wheel-running exercise. Neuronal activation was assessed by measuring c-Fos expression in brain regions implicated in addiction including orbitofrontal cortex (OC), insular cortex (IC) paraventricular nucleus of the thalamus (PVT), intermediodorsal nucleus of the thalamus (IMD) and amygdala. Out of all the regions examined, only the basal amygdala (BA) of females exhibited a significant increase in c-Fos expression following toluene exposure in the N-acetylcysteine treatment condition. A sex-based comparison of the BAS showed that male SD rats exhibited significantly higher c-Fos expression than female rats across all treatment groups- specifically in the bilateral, left and right BA on NAC treatment. Other brain regions such as the IC and OFC displayed descriptive trends in both the NAC and exercise treatment groups, but did not reach statistical significance. The amygdala plays a role in emotional processing, fear, anxiety and is also linked to the core reward regions of the brain like the nucleus accumbens (NAc). It is involved in drug seeking behavior by linking emotional cues and drug consumption which may explain the increase in c-Fos expression of female SD rats exposed to toluene in the NAC treatment condition. The elevated c-Fos expression in the BA of males in the same treatment group may reflect a greater sensitivity to toluene compared to females. Our findings suggest that the brain responses to toluene and subsequent treatment interventions may be brain region-, sex-, and hemisphere-specific. Ongoing studies on other brain regions is currently being examined to assess c-Fos expression. 

Corresponding Author's Email Address: *kbbenjamin@up.edu.ph / **rbcena@up.edu.ph