Small Intestinal Bacterial and Fungal Overgrowth: Health Implications and Management Perspectives

Abstract

Background/objectives: Small Intestinal Bacterial Overgrowth (SIBO) and Small Intestinal Fungal Overgrowth (SIFO) are distinct yet often overlapping conditions characterized by an abnormal increase in microbial populations within the small intestine. SIBO results from an overgrowth of colonic bacteria, while SIFO is driven by fungal overgrowth, primarily involving Candida species. Both conditions present with nonspecific gastrointestinal (GI) symptoms such as bloating, abdominal pain, diarrhea, and malabsorption, making differentiation between SIBO and SIFO challenging. This review aims to elucidate the underlying mechanisms, risk factors, diagnostic challenges, and management strategies associated with SIBO and SIFO.

Methods: A comprehensive review of current literature was conducted, focusing on the pathophysiology, diagnostic modalities, and therapeutic approaches for SIBO and SIFO.

Results: SIBO is commonly associated with factors such as reduced gastric acid secretion, impaired gut motility, and structural abnormalities like bowel obstruction and diverticula. It is frequently diagnosed using jejunal aspirates (≥10⁵ colony forming units (CFUs)/mL) or breath tests. In contrast, SIFO is linked to prolonged antibiotic use, immunosuppression, and gut microbiome dysbiosis, with diagnosis relying on fungal cultures from small intestinal aspirates due to the absence of standardized protocols.

Conclusion: The clinical overlap and frequent misdiagnosis of SIBO and SIFO highlight the need for improved diagnostic tools and a multidisciplinary approach to management. This review emphasizes the importance of understanding the mechanisms behind SIBO and SIFO, how they relate to other health outcomes, and potential management strategies to optimize patient care and therapeutic outcomes.

Keywords: SIBO; SIFO; dysbiosis; gut microbiome; small intestinal bacterial overgrowth; small intestinal fungal overgrowth.

Figure 1

Core bacterial and fungal organisms in the small intestines play essential roles in maintaining gut health, including nutrient metabolism, angiogenesis, immune regulation, and energy homeostasis. An imbalance in these microbial communities can disrupt the relevant functions, contributing to gastrointestinal and systemic health issues. Created in BioRender (Toronto, Canada, publication license: https://BioRender.com/ry5flzn, accessed on 9 April 2025).

Figure 2

A normal, well-balanced microbiome supports healthy, tight junctions in the intestinal lining, maintaining its selective permeability. However, dysbiosis and pathogenic biofilm formation can compromise these tight junctions, allowing harmful substances to enter the bloodstream and trigger systemic inflammation. In SIBO, bacterial metabolites such as lipopolysaccharides (LPSs), hydrogen sulfide (H₂S), and methane disrupt epithelial integrity, contributing to increased permeability. In SIFO, fungal enzymes such as phospholipases and aspartic proteinases further exacerbate gut barrier dysfunction. This increased permeability, often referred to as “leaky gut”, is linked to chronic diseases, autoimmune disorders, and other inflammatory health issues associated with poor diet and gut microbiota imbalances. Created in BioRender (Toronto, Canada, publication license: https://BioRender.com/nlrx413, accessed on 9 April 2025).

Figure 3

Illustration of Candida virulence factors. (A) Scanning Electron Microscopy image of Candida showing its phenotypic plasticity either as oval-shaped budding cells or (B) thread-like structures called hyphae. (C) Microscopy image showing invasive growth of fungal hyphae, indicative of epithelial barrier damage in mouse model (image from Ghannoum [101]). (D) Biofilm formation of Candida demonstrating creation of complex structure that could invade and break down gastrointestinal (GI) lining (image from Ghannoum [102]). (E) Phospholipase production (blue dots) during Candida albicans invasion aids in fungi invasion of GI cell: magnification × 10,000 (image from Ghannoum [103]).