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The ability of microbial communities to modulate disease phenotypes is now well established, particularly in immune disorders. Approaches to treat such conditions through microbial interventions have therefore gained much interest in recent years. Fecal microbiome transplant (FMT) has emerged as a promising therapy refractory Clostridioides difficile infections, although its application to more complex diseases is less effective and remains challenging due to lack of standardization, safety concerns and regulatory aspects. The use of “vaginal seeding”, the transfer of maternal vaginal microbiota to newborns lacking specific microbes, faces even harder issues, since recipients are infants with a still immature immune system. Here, I will discuss recent work we have performed in studying the role of the microbiome in inflammatory conditions and our attempts at developing microbial therapeutics that can treat or prevent such diseases.