Role of the duodenal microbiota in functional dyspepsia

Abstract

Background: Functional dyspepsia (FD) is a common and debilitating gastrointestinal disorder attributed to altered gut-brain interactions. While the etiology of FD remains unknown, emerging research suggests the mechanisms are likely multifactorial and heterogenous among patient subgroups. Small bowel motor disturbances, visceral hypersensitivity, chronic microinflammation, and increased intestinal tract permeability have all been linked to the pathogenesis of FD. Recently, alterations to the gut microbiome have also been implicated to play an important role in the disease. Changes to the duodenal microbiota may either trigger or be a consequence of immune and neuronal disturbances observed in the disease, but the mechanisms of influence of small intestinal flora on gastrointestinal function and symptomatology are unknown.

Purpose: This review summarizes and synthesizes the literature on the link between the microbiota, low-grade inflammatory changes in the duodenum and FD. This review is not intended to provide a complete overview of FD or the small intestinal microbiota, but instead outline some of the key conceptual advances in understanding the interactions between altered gastrointestinal bacterial communities; dietary factors; host immune activation; and stimulation of the gut-brain axes in patients with FD versus controls. Current and emerging treatment approaches such as dietary interventions and antibiotic or probiotic use that have demonstrated symptom benefits for patients are reviewed, and their role in modulating the host-microbiota is discussed. Finally, suggested opportunities for diagnostic and therapeutic improvements for patients with this condition are presented.

Keywords: disorders of gut-brain interaction; dysbiosis; functional dyspepsia; functional gastrointestinal disorders; intestinal mucosa; microbiota; small intestinal bacterial overgrowth.

FIGURE 1

Proposed disease model for the pathogenesis of functional dyspepsia. 1. Antigen presentation to the small intestinal mucosa, including food macromolecules or microbial antigens. 2. Activation of eosinophils and mast cells through an immune cascade. 3. Local nerve sensitization and systemic immune activation leading to symptomatology. 4. Maintenance of a low‐grade state of inflammation through bidirectional gut–brain and brain–gut pathways [Image created in BioRender]

FIGURE 2

Taxonomy of the small intestinal microbiota across the four main bacterial phyla. Pictured are key intestinal microbial species from phylum–class–genus