Mitochondrial Function and Microbial Metabolites as Central Regulators of Intestinal Immune Responses and Cancer

Abstract

Energy and anabolic metabolism are essential for normal cellular homeostasis but also play an important role in regulating immune responses and cancer development as active immune and cancer cells show an altered metabolic profile. Mitochondria take a prominent position in these metabolic reactions. First, most key energetic reactions take place within or in conjunction with mitochondria. Second, mitochondria react to internal cues from within the cell but also to external cues originating from the microbiota, a vast diversity of associated microorganisms. The impact of the microbiota on host physiology has been largely investigated in the last decade revealing that the microbiota contributes to the extraction of calories from the diet, energy metabolism, maturation of the immune system and cellular differentiation. Thus, changes in the microbiota termed dysbiosis have been associated with disease development including metabolic diseases, inflammation and cancer. Targeting the microbiota to modulate interactions with the mitochondria and cellular metabolism to delay or inhibit disease development and pathogenesis appears an attractive therapeutic approach. Here, we summarize recent advances in developing the therapeutic potential of microbiota-mitochondria interactions for inflammation and cancer.

The Gut-Wrenching Effects of Cryptosporidiosis and Giardiasis in Children

“…As part of the physiological process associated with growth, the infant’s gut microbiota undergoes several changes that can be influenced by genetic, nutritional, and environmental factors and are vastly different from one child to the other. The proper establishment of a healthy microbiota community at an early age can therefore determine the degree of susceptibility and/or resistance to intestinal illnesses through efficient cell signaling directed by microbial flora metabolic byproducts [ 95 ]. Abnormal alterations in intestinal bacterial metabolic activities can affect cryptosporidiosis and giardiasis diarrhea progression based on the degree of gut dysbiosis, or microbial imbalance, in the host [ 91 , 96 ].…”

Epithelial Dual Oxidase 2 Shapes the Mucosal Microbiome and Contributes to Inflammatory Susceptibility

“…All these bacteria [62][63][64] produce the short-chain fatty acid butyrate, an anti-inflammatory mediator with pleiotropic effector mechanisms that showed beneficial prospects in clinical intervention studies for IBD [18,65]. However, although associations between DUOX2 status and changes in the microbiome in IBD patients suggest a role in disease pathogenesis, direct functional studies are needed to clarify this issue.…”