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The gut is the largest immune organ in the body (78), harboring 70–80% of the body’s immune cells (79)

The human gut microbiome is characterized by trillions of microbes that possess 150-fold more protein-coding genes than the human genome (38, 39).

Unlike the human genome, which is largely fixed, the gut microbiome is plastic and can be affected by diet (12), past and present diseases (41), lifestyle factors such as exercise (42) and stress (43), or environmental exposures (44).

The gut has the dual and opposing roles of allowing nutrients to enter the body while excluding the entry of harmful substances.

A study comparing a standard rodent diet (fiber from wheat, corn, and oats comprising 4.3% of the diet by weight) with a diet devoid of any fiber showed that mice fed the fiber-deficient diet had a thinner mucus layer, thus allowing microbes to come in closer proximity to the gut epithelium (61).

SCFAs (short change fatty acid) resulting from the fermentation of DF (dietary fiber) have been shown to bolster gut barrier function by increasing gut cell proliferation and differentiation (62). SCFAs decrease intestinal pH, which can alter the gut microbiota by inhibiting the growth of pathogens and reduce the expression of microbial virulence genes (63).

In addition to affecting physical barriers, DF can also alter gut immune factors. The gut is the largest immune organ in the body (78), harboring 70–80% of the body’s immune cells (79)

In addition to altering physical barriers and intestinal immune function to minimize harm from microbe-derived proinflammatory factors, DF can also protect key organs such as the liver and kidney from metabolic insults.

DF may also affect liver metabolism by altering bile acid pools. Bile acids aid in the absorption of dietary fat and fat-soluble vitamins (107) as well as serve as signaling molecules (108). Primary bile acids are made by the host in the liver and secondary bile acids are generated by the gut microbiota.

One mechanism underlying kidney effects of DF may involve a decrease in the nitrogen load on the liver and the kidneys by increasing microbial biomass, which serves to sequester nitrogen in the gut and reduce the amount that enters the portal circulation (140).

The molecular signals involved in DF-associated alterations in host systems remain largely unknown, and the integrated networks that modulate diet-microbiome-host crosstalk remain to be fully elaborated.

Fiber-induced gut changes can result in enhanced gut barrier function that protects the liver and kidney from translocation of proinflammatory bacteria and bacterial products. This could allow the liver and kidneys to devote more capacity to metabolism-associated processes rather than controlling inflammation (104). In addition, DF increases microbial sequestration of nitrogen in the gut, resulting in increased fecal nitrogen excretion and reduced concentrations of nitrogenous metabolites in the blood. Reduced nitrogenous burden on the kidneys is desired for the treatment of diseases such as CKD.