Natural antibodies (Abs), produced in response to bacterial gut microbiota, drive resistance to infection in vertebrates. In natural systems, gut microbiota diversity is expected to shape the spectrum of natural Abs and resistance to parasites. This hypothesis has not been empirically tested. In this ‘Hypothesis and Theory’ paper, we propose that enteric microbiota diversity shapes the immune response to the carbohydrate α-Gal and resistance to avian malaria. We further propose that anti-α-Gal Abs are transmitted from mother to eggs for early malaria protection in chicks. Microbiota modulation by anti-α-Gal Abs is also proposed as a mechanism favoring the early colonization of bacterial taxa with α1,3-galactosyltransferase (α1,3GT) activity in the bird gut. Our preliminary data shows that bacterial α1,3GT genes are widely distributed in the gut microbiome of wild and domestic birds. We also showed that experimental infection with the avian malaria parasite P. relictum induces anti-α-Gal Abs in bird sera. The bird-malaria-microbiota system allows combining field studies with infection and transmission experiments in laboratory animals to test the association between microbiota composition, anti-α-Gal Abs, and malaria infection in natural populations of wild birds. Understanding how the gut microbiome influences resistance to malaria can bring insights on how these mechanisms influence the prevalence of malaria parasites in juvenile birds and shape the host population dynamics.