ro13-9904 and Obesity

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.. 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.. 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.. 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.

Topics: Adjuvants, Pharmaceutic; Animals; Anti-Bacterial Agents; Ceftriaxone; Dysbiosis; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Intestinal Absorption; Lactobacillus gasseri; Mice; Mice, Inbred C57BL; Obesity; Probiotics; Risk Assessment

The development of adjuvant therapies for obesity treatment is justified by the high prevalence of this disease worldwide, and the relationship between obesity and intestinal microbiota is a promising target for obesity treatment. Therefore, this study aimed at investigating the adjuvant treatment of obesity through the use of potential probiotics and antibiotics, either separately or sequentially. In the first phase of the experiment, animals had diet-induced obesity with consumption of a high saturated fat diet and a fructose solution. After this period, there was a reduction in caloric supply, that is the conventional treatment of obesity, and the animals were divided into 5 experimental groups: control group (G1), obese group (G2), potential probiotic group (G3), antibiotic group (G4), and antibiotic followed by potential probiotic group (G5). The adjuvant treatments lasted 4 weeks and were administered daily, via gavage: Animals in G1 and G2 received distilled water, the G3 obtained Lactobacillus gasseri LG-G12, and the G4 received ceftriaxone. The G5 received ceftriaxone for 2 weeks, followed by the offer of Lactobacillus gasseri LG-G12 for another 2 weeks. Parameters related to obesity, such as biometric measurements, food consumption, biochemical tests, histological assessments, short-chain fatty acids concentration, and composition of the intestinal microbiota, were analyzed. The treatment with caloric restriction and sequential supply of antibiotics and potential probiotics was able to reduce biometric measures, increase brown adipose tissue, and alter the intestinal microbiota phyla, standing out as a promising treatment for obesity.

Topics: Adipose Tissue, Brown; Anti-Bacterial Agents; Biometry; Ceftriaxone; Gastrointestinal Microbiome; Humans; Obesity; Probiotics

The aim of this study was to test whether the perioperative composition of intestinal microbiota can contribute to variable outcomes following vertical sleeve gastrectomy (VSG).. Although bariatric surgery is the most effective treatment for obesity, metabolic outcomes are variable.. Diet-induced obese mice were randomized to VSG or sham surgery, with or without exposure to antibiotics that selectively suppress mainly gram-positive (fidaxomicin, streptomycin) or gram-negative (ceftriaxone) bacteria on postoperative days (POD) 1-4. Fecal microbiota was characterized before surgery and on POD 7 and 28. Mice were metabolically characterized on POD 30-32 and euthanized on POD 35.. VSG resulted in weight loss and shifts in the intestinal microbiota composition relative to sham-operated mice. Antibiotic exposure resulted in sustained reductions in alpha (within-sample) diversity of microbiota and shifts in its composition. All antibiotic treatments proved to be detrimental to metabolic VSG outcomes, regardless of antimicrobial specificity of antibiotics. These effects involved functionally distinct pathways. Specifically, fidaxomicin and streptomycin markedly altered hepatic bile acid signaling and lipid metabolism, while ceftriaxone resulted in greater reduction of key antimicrobial peptides. However, VSG mice exposed to antibiotics, regardless of their specificity, had significantly increased subcutaneous adiposity and impaired glucose homeostasis without changes in food intake relative to control VSG mice.. Dysbiosis induced by brief perioperative antibiotic exposure attenuates weight loss and metabolic improvement following VSG. Potential mechanisms include disruption of bile acid homeostasis and reduction in the production of gut antimicrobial peptides. Results of this study implicate the intestinal microbiota as an important contributor to metabolic homeostasis and a potentially modifiable target influencing clinical outcomes following VSG.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Disease Models, Animal; Fidaxomicin; Gastrectomy; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Obesity; Streptomycin; Treatment Failure; Weight Loss

The aim of this study was to determine demographic and clinical features in children diagnosed with gallstones, risk factors for gallstone formation, the effectiveness of ursodeoxycholic acid therapy, and the course of the disease.. Patients aged 0-18 years were followed up for at least 6 months after the diagnosis of gallstones with ultrasonography and were evaluated retrospectively. Patients were evaluated with respect to age, sex, presenting symptoms, BMI, facilitating factors, accompanying diseases, family history of gallstones, history of ceftriaxone use, laboratory tests, ultrasonography findings and follow-up, and therapeutic approaches and results.. The study was completed with 70 patients. Thirty-nine (55.7%) patients were females. The mean age of the patients was 9.3±5.29 (0.3-18) years. The mean age among females was statistically significantly higher than that among males (P=0.007).No risk factor for stone formation was encountered in 50% of cases, whereas a family history of gallstones was present in 17.1%. Use of ceftriaxone was present in 8.6% of cases, total parenteral nutrition in 10%, obesity in 5.7%, hereditary spherocytosis in 4.3%, and Down's syndrome in 4.3%. The probability of dissolution of stones was 3.6 times higher in patients with stone sizes up to 5 mm [odds ratio (OR): 3.65, P=0.020], 3.9 times higher in those aged younger than 2 years (OR: 3.92, P=0.021), and 13.9 times higher in those with a single stone (OR: 13.97, P=0.003).. Our findings show that unknown causes are still prevalent in stone formation and that ursodeoxycholic acid exerts no effect on stone dissolution; however, diagnosis at younger than 2 years of age, a single stone, and small size of stone are factors affecting dissolution.

Topics: Adolescent; Age Distribution; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cholagogues and Choleretics; Cholecystectomy; Family; Female; Follow-Up Studies; Gallstones; Humans; Infant; Male; Medical History Taking; Obesity; Parenteral Nutrition, Total; Prognosis; Retrospective Studies; Risk Factors; Sex Distribution; Treatment Outcome; Ursodeoxycholic Acid

A 23-year-old gentleman with no significant medical history other than obesity was admitted with a history of balance problems, double vision and strange behaviour following a fall from bed. Systems examination was unremarkable. The patient was given intravenous acyclovir and intravenous ceftriaxone given the suspicion of encephalitis/meningitis. Investigations including routine bloods, CT/MRI Head and lumbar puncture were unremarkable. Within 48 h of commencing intravenous acyclovir, there was a marked deterioration in renal function. On stopping acyclovir therapy, renal function improved back to baseline. No other cause for deterioration in renal function was identified. The most likely cause for acute renal failure was secondary to acyclovir therapy. This has been well documented and is due to intratubular crystal precipitation. Moreover, in this case nephrotoxicity is likely secondary to the large boluses of intravenous acyclovir that had been given as prescribed according to the total body weight.

Topics: Accidental Falls; Acute Kidney Injury; Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Ceftriaxone; Encephalitis; Humans; Male; Meningitis; Obesity; Young Adult

Topics: Adrenal Cortex Hormones; Adrenergic Agonists; Anaphylaxis; Anti-Bacterial Agents; Atropine; Bronchodilator Agents; Ceftriaxone; Diabetes Mellitus, Type 2; Epinephrine; Fatal Outcome; Humans; Intubation, Intratracheal; Male; Malpractice; Middle Aged; Multiple Trauma; Obesity; Skin Tests