According to Elie Metchnikoff, an originator of modern immunology, several pivotal functions for disease and health are provided by indigenous microbiota. Nonetheless, important mechanistic insights have been elucidated more recently, owing to the growing availability of DNA sequencing technology. There are 10 to 100 trillion symbiotic microbes (such as viruses, bacteria, and yeast) in each human gut microbiota. Both locally and systemically, the gut microbiota has been demonstrated to impact immune homeostasis. Primary B-cell immunodeficiencies (PBIDs) are a group of primary immunodeficiency diseases (PIDs) referring to the dysregulated antibody production due to either intrinsic genetic defects or failures in functions of B cells. Recent studies have found that PBIDs cause disruptions in the gut's typical homeostatic systems, resulting in inadequate immune surveillance in the gastrointestinal (GI) tract, which is linked to increased dysbiosis, which is characterized by a disruption in the microbial homeostasis. This study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the crosstalk between the gut microbiome and PBID, the factors shaping the gut microbiota in PBID, as well as the potential clinical approaches for restoring a normal microbial community.