Digestion and GI Problems by drmayfield | Mar 7, 2017 | Digestive and GI issues, Holistic Health, Immune System HealthCan microbiome issues cause fatigue? Absolutely! It’s one of the top causes of nutrient depletion and energy exhaustion. Your overall health begins in the GI tract, and your mood depends upon a healthy microbiome. Good health begins in the gut.