In any biological event, interactions between the different hierarchical levels of biological organisations challenge the systems biology approach in driving insights. Integrative methods in systems biology, capable of connecting multiple biological organisations and handling high-throughput information from these hierarchical levels, are required to address this challenge.
In this work, we propose generic methodologies for integrating hierarchical levels of biological organisations using systems theory and other mathematical modelling approaches to advance our understanding of how defects in human gut microbiota contribute to compromised health in various diseases.
This involves-
i) Investigating how toxins produced from gut dysbiosis, or an imbalance in the composition of the human gut, reach the brain and affect its normal functioning in neurodevelopmental disorders such as Autism Spectrum Disorder (ASD).
ii) A separate study is also conducted to investigate the survival/inhibition mechanism of the pathogen Vibrio cholera El Tor, which has a unique fermentation ability in a glucose-enriched environment and on infecting the human gut, which causes cholera disease.
In each case, we first define the necessary interaction conditions between different biological organisations and then map back to the individual mechanistic details. In contrast to previous approaches, the proposed methodology provides comprehensive models that aid in visualising the spread of abnormalities at various levels of biological organisation. Furthermore, however, these diverse human diseases have different origins of infection in the host gut, involving multiple levels of biological organisation in the pathogenesis. We will highlight the importance of preserving host gut homeostasis in order to improve disease conditions, which will be achieved by investigating the role of dietary intervention in the host gut.
Thus, our findings highlight the importance of integrative approaches in systems biology in developing in silico predictions with significant accuracy about the mechanistic understanding and therapeutic strategies for various human diseases.