Daily Intake of Household-Produced Milk Kefir on Salmonella Typhimurium Infection in C57BL/6 Mice: Mortality, Microbiota Modulation and Immunological Implications.

AIMS: Salmonellosis, a major global cause of diarrheal diseases, significantly impacts the intestinal microbiome. Probiotic-rich beverages, such as kefir, are increasingly utilized as alternative health-promoting beverages associated with various microbiota benefits. This study investigated the repercussions of daily consumption of household-produced milk kefir on Salmonella enterica serovar Typhimurium infection in C57BL-6 mice. METHODS AND RESULTS: Kefir consumption pre infection reduced the presence of inflammatory cells in the colon and altered the cytokine profile by reducing IL-10 and increasing IFN-γ. Despite reducing intestinal inflammation, kefir intake did not yield a prompt response to an acute infection caused by the aggressive pathogen Salmonella. This contributed to increased mortality in the mice, evidenced by higher fecal Salmonella counts post-infection. Metabarcoding analysis demonstrated that the use of kefir before infection increases butyric acid by the higher abundance of Lachnospiraceae and Prevotellaceae families and genus in feces, coupled with an increase in Muribaculaceae family and Bacteroides genus among infected kefir-treated mice. While kefir hinted at microbiota alterations reducing enterobacteria (Helicobacter), decrease IL-10, and increased IFN-γ, butyric acid on pre-infection, the beverage potentially facilitated the systemic translocation of pathogens, intensifying the infection's severity by altering the immune response. CONCLUSIONS: The use of kefir in the dosage of 10% w/v (109 CFU), for acute infections with Salmonella Typhimurium, may not be enough to combat the infection and worsen the prognosis, leaving the intestine less inflamed, favoring the replication and translocation of the pathogen. These findings underscore the importance of prudently evaluating the widespread use of probiotics and probiotic-rich beverages, especially during acute infections, given their potential association with adverse effects during these diseases.

Ceftriaxone causes dysbiosis and changes intestinal structure in adjuvant obesity treatment.

BACKGROUND: Obesity is still a worldwide public health problem, requiring the development of adjuvant therapies to combat it. In this context, modulation of the intestinal microbiota seems prominent, given that the composition of the intestinal microbiota contributes to the outcome of this disease. The aim of this work is to investigate the treatment with an antimicrobial and/or a potential probiotic against overweight. METHODS: Male C57BL/6J mice were subjected to a 12-week overweight induction protocol. After that, 4-week treatment was started, with mice divided into four groups: control, treated with distilled water; potential probiotic, with Lactobacillus gasseri LG-G12; antimicrobial, with ceftriaxone; and antimicrobial + potential probiotic with ceftriaxone in the first 2 weeks and L. gasseri LG-G12 in the subsequent weeks. RESULTS: The treatment with ceftriaxone in isolated form or in combination with the potential probiotic provided a reduction in body fat. However, such effect is supposed to be a consequence of the negative action of ceftriaxone on the intestinal microbiota composition, and this intestinal dysbiosis may have contributed to the destruction of the intestinal villi structure, which led to a reduction in the absorptive surface. Also, the effects of L. gasseri LG-G12 apparently have been masked by the consumption of the high-fat diet. CONCLUSIONS: The results indicate that the use of a ceftriaxone in the adjuvant treatment of overweight is not recommended due to the potential risk of developing inflammatory bowel disease.

Dibenzoylmethane derivative inhibits melanoma cancer in vitro and in vivo through induction of intrinsic and extrinsic apoptotic pathways.

Malignant melanoma has a low incidence, but is the most lethal type of skin cancer. Studies have shown that dibenzoylmethanes (DBMs) have interesting biological activities, including antineoplastic properties. These findings led us to investigate whether news DBM derivatives exert antitumor effects against skin cancers. In a previous study, we found that 1,3-diphenyl-2-benzyl-1,3-propanedione (DPBP) has high in vitro antineoplastic activity against murine B16F10 melanoma cells, with an IC50 of 6.25 µg/mL. In the current study, we used transdermal and topical formulations of DPBP to evaluate its activity and molecular mechanism of action in a murine model of melanoma. The compound induces tumor cell death with high selectivity (selectivity index of 41.94) by triggering apoptosis through intrinsic and extrinsic pathways. DPBP treatment reduced tumor volume as well as serum VEGF-A and uric acid levels. Hepatomegaly and nephrotoxicity were not observed at the tested doses. Histopathological analysis of sentinel lymph nodes revealed no evidence of metastases. According to the observed data, the DPBP compound was effective for the topical treatment of melanoma cancer, suggesting that it acts as a chemotherapeutic or chemopreventive agent.