Ginger As A Microbiome Modulator

Derived from the root of the flowering Zingiber officinale plant, ginger is a common spice that also has a long history as a medicinal botanical. Much of its medicinal effect has been attributed to a natural oil called gingerol that has both anti-inflammatory and antioxidant properties. Inflammation and oxidation are risk factors that promote many chronic conditions, and ginger’s ability to counteract these factors may be the basis for how ginger improves health. While the data are still limited and not definitive, consumption of ginger has been shown in some studies to help relieve muscle soreness, improve osteoarthritis pain, lower LDL cholesterol (the “bad” cholesterol), reduce heart disease, and improve brain function. Additionally, ginger has a strong ability to reduce nausea and improve digestion, though the biochemical basis for these effects is not well defined. Still, this potential for broadly improving health makes ginger an attractive nutraceutical for further study.

A study by Teng et al. in the journal “Cell Host & Microbe” reveals a novel mechanism by which ginger and other food products can use exosome-like nanoparticles (ELNs) and microRNAs (miRNAs) to exert some of their effects. ELNs are minute lipid vesicles (also called liposomes) that ferry materials between cells. In both plants and animals, these microscopic ELN particles are spheres produced within a cell that are packed with proteins and nucleic acids, including miRNAs. After production, ELNs are then excreted from the cells where they can be taken up by surrounding cells or transported to distal portions of the plant. Once taken in by a new cell the cargo in the ELN is released and can influence changes in the recipient cell. Among the various types of modifying cargos, miRNAs are small RNAs that do not code for proteins. Instead, miRNAs act by binding to mRNAs (the RNAs that do code for proteins) and preventing the mRNAs from making protein. Thus, by preventing production, a miRNA can reduce the level of its target protein in recipient cells and change the characteristics of that cell.

What Teng et al. found was that ELNs from ginger carried miRNAs that can be preferentially taken up some bacteria in the gut. In particular, they observed that ginger ELNs were taken up by and promoted the growth of Lactobacilli, a group of bacteria that has beneficial properties in the gut. Furthermore, the miRNAs in the ginger ELNs activated a biochemical pathway in specific species known as Lactobacillus rhamnosus. The activated Lactobacillus rhamnosus produced a compound known as indole-3-carboxaldehyde (I3A) that caused colon cells to secrete a cytokine called IL-22. IL-22 promotes gut health by stimulating the growth of intestinal cells, reducing inflammation, and protecting against harmful bacteria. When mice with experimentally-induced colitis were fed the RNAs from ginger ELNs the colitis improved compared to the control mice, and the same result was obtained by feeding I3A to another group of test mice. This confirmed that the plant miRNAs had a physiological effect on the animals, likely mediated via their ability to increase I3A production by the gut microbiome.

The ability of diet to modify the composition of bacterial species in the gut is well known, and this study provides a mechanistic framework where ELNs in ginger deliver miRNA cargoes that promote the growth of select bacterial species. If these expanded bacterial populations produce beneficial compounds, such as induced by the ginger miRNAS, then gut health is improved. This is an exciting finding that expands our understanding of the diet-microbiome connection and suggests that we may be able to identify individual plant miRNAs that alter different aspects of gut physiology. Currently, we treat ourselves with natural botanicals, such as ginger root, containing complex mixtures of bioactive compounds with unknown properties and possibly conflicting or off-target effects. Instead, someday we may be able to use single compounds, such as individual miRNAs, as targeted dietary supplements to treat different types of bowel disorders and other ailments.

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