The study investigates the association between antibiotic use and microscopic colitis (MC), a characteristic change in the microbiome characterized by watery, non-bloody diarrhea. The research focused on a cohort of 2393 adults in Sweden, ages ≥65 years, with varying genders, who were prescribed antibiotics in 2007–2017. Between 14 and 1 week post-variable antibiotic use, the authors examined the incidence of MC. The primary outcome was the risk of MC during treatment and 3 post-treatment intervals compared with periods without treatment (nontreatment). Antibiotic use was prescribed on average for 1.6 weeks, predominantly phenoxymethylpenicillin (50%) and doxycycline (35%). The study also compared microbiological outcomes with individuals whose microbiota lacked MC, conducting a negative control analysis to assess antibiotic effects on microbiome changes. The findings suggest that prescribing antibiotics increases the risk of MC during treatment and post-treatment, particularly in women and older adults. The negative control analysis revealed similar risks of microbiome changes linked to antibiotic use. The study highlights potential detection bias in terms of microbiome changes in close to-clinical scenarios. These results emphasize the importance of monitoring microbiome changes during and after antibiotic use. The findings are significant for healthcare providers as they caution against ignoring microbiome changes due to potential associated Mc. The study also underscores the complex interplay between antibiotic use and microbial dynamics, emphasizing the need for careful and coordinated management of microbiome and antiviral therapy in patients with microbiome-related Cirrhosis. The results contribute to a better understanding of the microbiome-wielding patient population and provide a basis for improved monitoring and management of such gastrointestinal scenarios. Overall, the study offers new insights into the relationship between antibiotic use and microbiome changes, particularly in older adults and women, suggesting that the microbiome undergoes significant shifts in response to antibiotic treatment. These findings are critical for advancing comprehensive management strategies in antimicrobial resistance (AMR)-hotspot healthcare settings.