Diet plays an essential role in human development and growth, contributing to health and well-being. The socio-economic values, cultural perspectives, and dietary formulation in sub-Saharan Africa can influence gut health and disease prevention. The vast microbial ecosystems in the human gut frequently interrelate to maintain a healthy, well-coordinated cellular and humoral immune signalling to prevent metabolic dysfunction, pathogen dominance, and induction of systemic diseases. The diverse indigenous diets could differentially act as biotherapeutics to modulate microbial abundance and population characteristics. Such modulation could prevent stunted growth, malnutrition, induction of bowel diseases, attenuated immune responses, and mortality, particularly among infants. Understanding the associations between specific indigenous African diets and the predictability of the dynamics of gut bacteria genera promises potential biotherapeutics towards improving the prevention, control, and treatment of microbiome-associated diseases such as cancer, inflammatory bowel disease, obesity, type 2 diabetes, and cardiovascular disease. The dietary influence of many African diets (especially grain-base such as millet, maize, brown rice, sorghum, soya, and tapioca) promotes gut lining integrity, immune tolerance towards the microbiota, and its associated immune and inflammatory responses. A fibre-rich diet is a promising biotherapeutic candidate that could effectively modulate inflammatory mediators’ expression associated with immune cell migration, lymphoid tissue maturation, and signalling pathways. It could also modulate the stimulation of cytokines and chemokines involved in ensuring balance for long-term microbiome programming. The interplay between host and gut microbial digestion is complex; microbes using and competing for dietary and endogenous proteins are often attributable to variances in the comparative abundances of Enterobacteriaceae taxa. Many auto-inducers could initiate the process of quorum sensing and mammalian epinephrine host cell signalling system. It could also downregulate inflammatory signals with microbiota tumour taxa that could trigger colorectal cancer initiation, metabolic type 2 diabetes, and inflammatory bowel diseases. The exploitation of essential biotherapeutic molecules derived from fibre-rich indigenous diet promises food substances for the downregulation of inflammatory signalling that could be harmful to gut microbiota ecological balance and improved immune response modulation.
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