Gut bacteria play an essential role in the human body by regulating multiple functions, producing essential metabolites, protecting against pathogen invasion, and much more. Conversely, changes in their community structure are linked to several gastrointestinal (GI) and non-GI conditions. Fortunately, these bacteria are amenable to external perturbations, but we need specific tools for their safe manipulation as nonspecific changes can cause unpredicted long-term consequences. Here, we mainly discuss recent advances in cultivation-independent technologies and argue their relevance to different key steps, that is, identifying the modulation targets and developing phage-based tools to precisely modulate gut bacteria and restore a sustainable microbiome in humans. We finally suggest multiple modulating strategies for different dysbiosis-associated diseases.
HighlightsMicrobiome manipulation should be precise to avoid unwanted consequencesphages may provide a solution due to their host-specific nature.It is essential to shift from classical isolation and characterisation methods to novel culture-independent techniques to discover the full potential of phages as microbiome modulators. New culturing technologies enable mechanistic studies of yet-to-becultured gut bacteria, providing insight into their physiology and network interactions.Multi-omics are more accurate than mono-omics in identifying bacterial taxa and functional traits related to human health and disease.