Probiotics in Disease Prevention and Treatment

Abstract

Few treatments for human diseases have received as much investigation in the past 20 years as probiotics. In 2017, English-language meta-analyses totaling 52 studies determined the effect of probiotics on conditions ranging from necrotizing enterocolitis and colic in infants to constipation, irritable bowel syndrome, and hepatic encephalopathy in adults. The strongest evidence in favor of probiotics lies in the prevention or treatment of 5 disorders: necrotizing enterocolitis, acute infectious diarrhea, acute respiratory tract infections, antibiotic-associated diarrhea, and infant colic. Probiotic mechanisms of action include the inhibition of bacterial adhesion; enhanced mucosal barrier function; modulation of the innate and adaptive immune systems (including induction of tolerogenic dendritic cells and regulatory T cells); secretion of bioactive metabolites; and regulation of the enteric and central nervous systems. Future research is needed to identify the optimal probiotic and dose for specific diseases, to address whether the addition of prebiotics (to form synbiotics) would enhance activity, and to determine if defined microbial communities would provide benefit exceeding that of single-species probiotics.

Keywords: allergy; diarrhea; immunology; lactobacillus; microbiome; regulatory T cells.

Figure 1.

Major phyla in prospective multicenter study of microbiota of premature neonates during the first 60 days of life. Bar graphs show evolution toward increased negativicutes in control group, as contrasted to increased gamma proteobacteria in those developing NEC. From Warner et al.

Figure 2.

Two-dimensional principal components. Microbiota in IBS (A), divided by subgroup (B) in which C refers to constipation, D refers to diarrhea, and M refers to mixed diarrhea and constipation. From Pozuelo et al.

Figure 3.

Documented mechanisms of action of probiotics. Probiotics may inhibit pathogenic bacterial adhesion, enhance barrier function, and interact with TLRs expressed on the intestinal epithelial cells and dendritic cells to produce cytokines/chemokines to further modulate T cells. Probiotics also can produce bioactive metabolites and affect nervous system subsequently modulate gut motility, reduce pain, and involve in gut-brain function (Illustration by Liu, Y.).

Figure 4.

Lactobacillus reuteri DSM 17938 treatment increases survival (A) and reduces inflammation (B) in organs of SF mice (arrows indicate lymphocyte infiltration). From He et al.

Figure 5.

Mechanisms of Lactobacillus reuteri DSM 17938 protection against Treg-deficiency-mediated autoimmunity. Treg deficiency shapes gut microbiota and induces autoimmunity resulting in multi-organ inflammation and early death (left). Lactobacillus reuteri DSM 17938 remodels gut microbiota, alters the metabolites (inosine) and protects against Treg-deficiency-induced autoimmunity by suppressing T_H1/T_H2 cells via inosine-adenosine A2A interaction (right). From He et al.