Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation

Abstract

Recent explorations of the human gut microbiota suggest that perturbations of microbial communities may increase predisposition to different disease phenotypes. Dietary nutrients may be converted into metabolites by intestinal microbes that serve as biologically active molecules affecting regulatory functions in the host. Probiotics may restore the composition of the gut microbiome and introduce beneficial functions to gut microbial communities, resulting in amelioration or prevention of gut inflammation and other intestinal or systemic disease phenotypes. This review describes how diet and intestinal luminal conversion by gut microbes play a role in shaping the structure and function of intestinal microbial communities. Proposed mechanisms of probiosis include alterations of composition and function of the human gut microbiome, and corresponding effects on immunity and neurobiology.

Keywords: Lactobacillus; diet; gut microbiota; immunomodulation; nervous system; probiotics.

Conflict of interest statement

Conflict of interest statement: J.Versalovic received unrestricted research support from Biogaia AB (Stockholm, Sweden).

Figures

Figure 1.

A recent metatranscriptomic analysis determined the distribution of functional roles of human fecal microbiota. This study demonstrated the distribution of Clusters of Orthologous Groups (COGs) categories across each of the 10 metatranscriptomes (A, B, C, D, E, F, K, L, N and O) that were sequenced. (Adapted from Gosalbes et al. [2011].)

Figure 2.

Luminal conversion by intestinal microbes may play an important role in host–microbiota interactions. Orally consumed nutrients may be converted by intestinal microbes into bioactive compounds that could affect the health of the host and the intestinal microbiota. GABA, gamma-aminobutyric acid; SCFAs, short-chain fatty acids.

Figure 3.

Probiotic mechanisms in the human gastrointestinal tract. Probiotics may manipulate intestinal microbial communities and suppress growth of pathogens by inducing the host’s production of β-defensin and IgA. Probiotics may be able to fortify the intestinal barrier by maintaining tight junctions and inducing mucin production. Probiotic-mediated immunomodulation may occur through mediation of cytokine secretion through signaling pathways such as NFκB and MAPKs, which can also affect proliferation and differentiation of immune cells (such as T cells) or epithelial cells. Gut motility and nociception may be modulated through regulation of pain receptor expression and secretion of neurotransmitters. APRIL, a proliferation-inducing ligand; hsp, heat shock protein; IEC, intestinal epithelial cell; Ig, immunoglobulin; MAPK, mitogen-activated protein kinase; NFκB, nuclear factor-kappaB; pIgR, polymeric immunoglobulin receptor; STAT, signal transducer and activator of transcription; Treg, T regulatory cell. (Reproduced with permission from Thomas and Versalovic [2010].)

Figure 4.

Mechanisms of immunomodulation by beneficial microbes. Probiotics can modulate the immune system in the intestine through the luminal conversion process. The bacteria produce secreted soluble factors and metabolites, such as short-chain fatty acids (SCFAs) and vitamins using substrates from the diet. These bioactive compounds affect the function of intestinal epithelium and mucosal immune cells, resulting in production of cytokine and related factors such as a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF). (Adapted from Preidis and Versalovic [2009].)

Figure 5.

Proposed interactions between the gut microbiota, the intestinal tract, the central and peripheral nervous systems and the immune system. Intestinal microbes may interact with intestinal epithelial cells or immune cells directly or they can produce bioactive compounds and neurotransmitters to modulate immunity or the gut–brain axis. These intricate and complex interactions result in signaling to the central nervous system. CRH, corticotropin-releasing hormone; ACTH, adrenocorticotropic hormone; IDO, indoleamine-pyrrole 2,3-dioxygenase. (Reproduced with permission from Bienenstock and Collins [2010].)