The gut microbiome inside the human intestine is a highly versatile ecosystem and is recognized as an integral element to human health and disease. It contributes to host physiological processes, including host intestinal barrier integrity, immunological fitness, and metabolic fitness, and responds dynamically. Abnormalities in the normal composition of the gut microbiome i.e., Gut dysbiosis also have been reported to influence remote organ normal functioning. To cater to the need of patient-specific medicine and suggest therapeutic strategies it is required to model the complex interactions between the gut microbiome and observable disease symptoms with the help of emerging data-driven approaches. Constraint-based reconstruction and analysis (COBRA) are one of the preferred systems biology methods based on Omics data to study biological cell systems with mechanistic details. However, COBRA operates on steady-state conditions, hence, to capture the dynamics of disease pathogenesis a whole-body physiologically based pharmacokinetic (PBPK) modeling approach is required, specifically to model the transport and effect of gut-derived toxins. In this work a novel model building strategy i.e., the integration of COBRA and PBPK models is developed. The framework provides both qualitative and quantitative aspects of pathogenic factors and treatment thereof, for several diseases that show strong association with gut microbiota. We include a case study of Autism spectrum disorder, a chronic kidney disease that is reported to be strongly associated with gut dysbiosis in recent research. Also, Vibrio cholera interaction with gut microbiome in cholera disease. In conclusion, these efforts ultimately aim to develop data-driven effective modeling approaches to rehabilitate perturbed human microbial ecosystems to restore human health or prevent disease.