ABSTRACT
AIMS: To examine whether co-administration of intestinal alkaline phosphatase (IAP) with antibiotics early in life may have a preventive role against metabolic syndrome (MetS) in mice. METHODS: A total of 50 mice were allocated to four treatment groups after weaning. Mice were treated with azithromycin (AZT) ± IAP, or with no AZT ± IAP, for three intermittent 7-day cycles. After the last treatment course, the mice were administered a regular chow diet for 5 weeks and subsequently a high-fat diet for 5 weeks. Body weight, food intake, water intake, serum lipids, glucose levels and liver lipids were compared. 16S rRNA gene pyrosequencing was used to determine the differences in microbiome composition. RESULTS: Exposure to AZT early in life rendered mice susceptible to MetS in adulthood. Co-administration of IAP with AZT completely prevented this susceptibility by decreasing total body weight, serum lipids, glucose levels and liver lipids to the levels of control mice. These effects of IAP probably occur as a result of changes in the composition of specific bacterial taxa at the genus and species levels (e.g. members of Anaeroplasma and Parabacteroides). CONCLUSIONS: Co-administration of IAP with AZT early in life prevents mice from susceptibility to the later development of MetS. This effect is associated with alterations in the composition of the gut microbiota. IAP may represent a novel treatment against MetS in humans.
Subject(s)
Alkaline Phosphatase/therapeutic use , Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , Dietary Supplements , Dysbiosis/prevention & control , Intestinal Mucosa/enzymology , Metabolic Syndrome/prevention & control , Acholeplasma/classification , Acholeplasma/drug effects , Acholeplasma/growth & development , Acholeplasma/isolation & purification , Alkaline Phosphatase/adverse effects , Animals , Bacteroides/classification , Bacteroides/drug effects , Bacteroides/growth & development , Bacteroides/isolation & purification , Cattle , Diet, High-Fat/adverse effects , Dietary Supplements/adverse effects , Dysbiosis/chemically induced , Dysbiosis/microbiology , Dysbiosis/physiopathology , Feces/microbiology , Gastrointestinal Microbiome/drug effects , Male , Metabolic Syndrome/complications , Metabolic Syndrome/etiology , Metabolic Syndrome/microbiology , Mice, Inbred C57BL , Molecular Typing , Obesity/complications , Obesity/etiology , Obesity/microbiology , Obesity/prevention & control , Weaning , Weight Gain/drug effectsABSTRACT
Microsatellite instability in sporadic colorectal cancer patients was assessed, and the clinicopathological associations were evaluated in northeastern Iran, which is a high-risk region for gastrointestinal malignancies. Microsatellite instability (MSI) status of tumoral tissue, compared to normal tissue, was assessed with a standard panel of MSI markers on paraffin-embedded surgically resected tissues from 67 consecutive sporadic colorectal cancer patients. Eleven of the patients were under 40 years old. Female patients were significantly younger than male patients (mean age 54.2 vs 62.1 years, P = 0.020). MSI analysis revealed 18 cases of MSI-H (26.9%), 11 MSI-L (16.4%) and 38 MSS (microsatellite stable tumors; 56.7%). While a greater proportion of patients consisted of males, 56.7 vs 43.3% females, MSI-H was more frequent in females (34.5 vs 21.5%). MSI was associated with proximal location of tumor (P = 0.003) and lower stages of tumor (P = 0.002), while MSS tumors were associated with node metastasis. MSI has a higher frequency in sporadic colorectal cancer patients, suggesting that molecular epidemiology of the genetic alterations involved in colorectal cancer carcinogenesis has a different pattern in the Iranian population, which deserves further epidemiological attention. The high frequency of MSI-H in this population suggests that we should look at microsatellite instability prior to chemotherapy to determine the most appropriate chemotherapeutic strategy in our population.
