S. gallolyticus (a member of SBSEC) is part of the gut microbiota and a significant pathogen in both humans (linked with IE and CRC) and animals (systemic infection in ruminants, pigs, and turkeys), with trending host predilections and differences of pathogenicity between each member of SBSEC.

Streptococcus gallolyticus belongs to the Streptococcus bovis/Streptococcus equinus complex (SBSEC) and the S. bovis group (Schlegel et al., 2003). S. gallolyticus is part of the gut microbiota and an opportunistic pathogen, causing systemic infectious diseases and deaths in humans and animals (Figure 1). The strong link between S. gallolyticus and human infective endocarditis (IE), combined with the frequent bacteremia in colorectal cancer (CRC) patients, raises questions about its potential role in bacterial-induced cancer development. S. gallolyticus was not traditionally considered highly relevant in veterinary medicine. However, recent findings indicate a growing clinical significance. This includes emerging outbreaks of Streptococcus gallolyticus subsp. pasteurianus (Sgp) as a primary pathogen in turkey (Gray et al., 2023) and a causative agent of IE in pigs (Sitthicharoenchai et al., 2022). These prompt concerns about further understanding of bacterial pathogenesis and potential interspecies transmission, both animal-to-animal and animal-to-human. This review provides a comprehensive overview of S. gallolyticus, detailing its taxonomic classification, clinical presentation across various species, pathogenic mechanism, and current laboratory diagnostic methodologies. Furthermore, we will discuss the limitations of our understanding of S. gallolyticus and approach to fill the knowledge gaps.

Due to the high genomic diversity and the advent of modern molecular identification techniques, the taxonomy of S. gallolyticus has undergone several major reclassifications. To maintain clarity throughout this review, we use the broader term SBSEC when discussing findings from studies that refer to the bacteria as S. bovis or when specific species or subspecies differentiation within the complex is ambiguous.

Advances in molecular and biochemical techniques have led to multiple reclassifications of SBSEC (Table 1). Historically, S. gallolyticus was categorized as S. bovis biotype I and II, which belong to the Lancefield Group D non-enterococcal streptococci (Orla-Jensen, 1919). This subclassification of S. bovis was based on the mannitol-fermenting group (biotype I) and the mannitol-negative fermenting group (biotype II) (Facklam, 1972; Parker and Ball, 1976). Biotype II was further subdivided into biotypes II/1 (non-fermenting) and II/2 (fermenting trehalose) based on DNA hybridization and trehalose fermentation results (Coykendall and Gustafson, 1985; Coykendall, 1989).

Farrow et al. (1984) further proposed a classification into 1–6 DNA groups based on the DNA–DNA hybridization, including two novel species: S. saccharolyticus (group 5) and S. alactolyticus (group 6). The term SBSEC was later proposed by the same research group based on their findings and a comparable serologic typing system and physiological reactions of S. equinus from other researchers (Kilpper-Bälz et al., 1982; Hillman et al., 1989; Andrewes and Horder, 1906; Smith and Shattock, 1962).

In the early 1990s, phylogenetic classification based on small subunit rRNA sequences became widely used for differentiating streptococcal species (Bentley et al., 1991). S. saccharolyticus was reclassified to the genus Enterococcus (Rodrigues and Collins, 1990). Combining the method with biochemical analyses led to the identification of novel (sub)species within the SBSEC, including S. infantarius (Bouvet et al., 1997), S. macedonicus (Tsakalidou et al., 1998), S. waius (Schlegel et al., 1999), S. infantarius subsp. infantarius, and S. infantarius subsp. coli (Schlegel et al., 2000). In 1995, Osawa et al. demonstrated tannase production in S. bovis biotype I. This discovery led to S. bovis biotype I being renamed as S. gallolyticus (Osawa et al., 1995). Another tannase-producing bacterium in goats, S. caprinus, was also reclassified under S. gallolyticus (Brooker et al., 1994; Sly et al., 1997).

Using DNA-DNA hybridization, S. intestinalis was considered a synonym of S. alactolyticus (Vandamme et al., 1999). A sodA gene-based phylogenetic interference was proposed as a classification system by Poyart et al. (2002), confirmed the synonymous assignments, and identified novel clusters: S. lutetiensis (previously S. infantarius subsp. coli) and S. pasteurianus (previously S. bovis biotype II/2) (Poyart et al., 2002). Based on DNA–DNA reassociation, S. waius is now considered as S. macedonicus (Manachini et al., 2002). The current classification of SBSEC was established by Schlegel et al. (2003) using a combination of DNA–DNA hybridization, 16S rDNA sequencing, and biochemical tests. This classification system includes three subspecies of S. gallolyticus (S. gallolyticus subsp. gallolyticus Sgg), S. gallolyticus subsp. macedonicus, S. gallolyticus subsp. pasteurianus (Sgp), 1 subspecies of S. infantarius subsp. infantarius (Sii), and 3 separate species of S. lutetiensis, S. alactolyticus, and S. equinus (Schlegel et al., 2003).

Members of the SBSEC are commensal bacteria belonging to the phylum Firmicutes, a major component of healthy human gut microbiota (Hou et al., 2022; Jandhyala et al., 2015). Several studies have revealed a shift in gut microbiome diversity in CRC patients, and the contribution of intestinal commensal bacteria to tumor development (Ahn et al., 2013; Boleij et al., 2011; Thomas et al., 2019; Kim and Lee, 2022; Fusco et al., 2024; Paduraru et al., 2025). Specifically, reports have demonstrated that fecal carriage of SBSEC is higher in CRC patients compared to healthy individuals (Klein et al., 1977; Périchon et al., 2022), suggesting a link between S. gallolyticus and CRC pathogenesis.

The clinical association between CRC and IE was first documented by McCoy and Mason (1951). The prevailing hypothesis suggests that tumor growth compromises the intestinal barrier, which allows opportunistic gut commensal bacteria to enter the bloodstream and subsequently colonize the heart valves (Keusch, 1974). This connection is supported by clinical data showing that 25 to 80% of patients with SBSEC bacteremia also have concomitant (Abdulamir et al., 2011). Furthermore, the reported association rate between SBSEC IE and CRC across various studies ranges from 18 to 62% (Abdulamir et al., 2011). While various species within the SBSEC bacteremia are associated with CRC, results from blood culture isolates show the strongest link with Sgg and Sgp, and to a lesser extent, Sii (Sánchez et al., 2014). Independent of its association with CRC, SBSEC has ranked among the top five causes of IE globally since the early 2000s (Vogkou et al., 2016; Öberg et al., 2022). Within this complex, Sgg has continued to be the predominant pathogen responsible for these infections (Öberg et al., 2022).

The features of non-IE SBSEC infections have been reported sporadically; however, they have not been well defined. A 23-year retrospective study by Corredoira et al. (2014) investigated patients with biliary tract infections caused by SBSEC. It revealed that such infections resulting in cholangitis and cholecystitis are commonly associated with Sii and Sgp, accounting for 57 and 39% of 51 cases, respectively. The infection is often an ascending infection secondary to underlying blockage of the biliary tree (Lee et al., 2003; Corredoira et al., 2014). SBSEC is also associated with urinary tract infections (UTIs). The study, conducted from 1995 to 2012, shows that 45% of 88 patients with SBSEC bacteriuria were asymptomatic. The remaining patients display symptoms of lower UTIs (35%) or upper UTIs (20%) (Matesanz et al., 2014). Notably, Sgp is a dominant subspecies that infects urinary systems, and elderly women are predisposed to the infection (Clarridge et al., 2001; Fernández-Ruiz et al., 2010; Romero et al., 2011). Arthritis, osteomyelitis, and spondylodiscitis caused by SBSEC have been reported as complications associated with IE through septicemic spread (García-País et al., 2016). Moreover, arthritis can also be predisposed in patients with prosthetic joints, with Sgg responsible for 0.4% of 2,459 cases of prosthetic joint infection (Thompson et al., 2020). Lastly, neurological infections caused by SBSEC are sporadic, with meningitis reported in only 0.3–5% of cases and typically associated with other conditions. Other central nervous system (CNS) infections, such as abscesses and subdural empyema, are even less frequent (Cabellos et al., 1999; Sánchez et al., 2024; Baranda et al., 1985).

While SBSEC predominantly inhabits the gastrointestinal tract of ruminants and poultry, it can be detected in pigs, dogs, horses, and wildlife (Hodge and Sherman, 1937; Sillanpää et al., 2009; Maďar et al., 2021). Although sporadic opportunistic infections have long been recognized in various species, large-scale and cluster outbreaks of this bacterium cause significant economic losses in livestock and have raised concerns, highlighting the need for greater attention to it in veterinary medicine (Park et al., 2021; Sitthicharoenchai et al., 2022; Gray et al., 2023). The following section will detail the importance of SBSEC in various domestic animal species.

SBSEC comprises a group of bacteria that can be readily grown on routine aerobic bacterial culture from clinical samples. The colony morphology on blood agar is small, gray, and exhibits γ-hemolysis. On microscopic examination, the bacteria are gram-positive, diplococci to chain-forming cocci. Common laboratory identification methods for SBSEC include biochemical testing, sequencing of the 16S rRNA and sodA genes (Poyart et al., 2002; Romero et al., 2011), as well as matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI-TOF MS) platforms. However, a single platform to accurately identify all SBSEC species and subspecies is not currently available. This difficulty arises from the high genetic conservation within the complex; for example, the 16S rRNA gene is nearly identical between some members of SBSEC (Jans et al., 2015). Recent data indicate that subspeciation of S. gallolyticus is most reliably achieved through sodA sequencing and the Vitek MS MALDI-TOF platform (Putnam et al., 2023). The ability to accurately identify SBSEC to the subspecies level is clinically important for the diagnosis of Sgg-associated IE and CRC, and its significance is increasing in veterinary medicine. Multiplex quantitative polymerase chain reaction (qPCR) has been developed to identify clinically significant SBSEC subspecies (Lopes et al., 2014). However, a limited number of samples were tested, and the sensitivity and specificity of this qPCR assay are unclear. Thus, there is a need for research efforts to improve and develop more robust diagnostic tools for the identification and classification of SBSEC. Until then, we recommend that diagnostic laboratories report isolates as SBSEC, followed by the species/subspecies or undetermined, accompanied by a statement outlining the limitations of the testing method used.

Multiplex antibody detection of Sgg pilus antigens has been developed in research settings for detecting preneoplastic stages of CRC. While results indicate that individuals with detectable Sgg antibody face a 40% increased risk of developing CRC within 10 years (Butt et al., 2018), the clinical utility is currently limited by the low assay sensitivity (16 to 43%) for early detection of CRC (Boleij et al., 2012). Therefore, these antibody results should be interpreted in conjunction with other robust diagnostic methods for CRC.

Streptococcus gallolyticus infection is a multifaceted issue in both human and veterinary medicine. It is a recognized etiology of IE in humans and is strongly associated with CRC. Concurrently, it has become an emerging pathogen in various production animals, inflicting significant economic losses. Despite its established role in certain species, such as septicemia in turkeys, bovine mastitis, and swine IE, our understanding of the pathogenesis remains limited. Significant knowledge gaps remain regarding predisposing host conditions, the specific determinants of pathogenicity, and the extent of genomic variation among isolates from different animal species. While multiple virulence factors have been identified in human isolates of S. gallolyticus, their prevalence and function in animal clinical isolates have not been thoroughly investigated. Furthermore, the potential for zoonotic transmission of pathogenic strains and the challenge of antimicrobial resistance are of growing concern. Individuals with occupational exposure, such as farm workers and abattoir employees, or individuals who consume raw meat and dairy products, may be at a higher risk of infection.

Complicating this epidemiological assessment is the evolving taxonomy of the SBSEC, to which S. gallolyticus belongs. Studies have demonstrated that different species and subspecies within SBSEC displayed distinct host predilections and potential differences in pathogenicity. However, the frequent taxonomical revisions have affected the precise tracking of clinical prevalence and incidence data for individual species and subspecies of SBSEC. Furthermore, variations in diagnostic techniques employed by different laboratories for SBSEC identification and how the laboratory reports the results (as a complex or by species/subspecies) complicate the establishment of retrospective epidemiological data.

To fill this knowledge gap, future research should prioritize the standardization of the laboratory diagnostic methods, coupled with adopting the species- or subspecies-specific reporting as a foundational step that would significantly enhance our understanding of the clinical significance of individual SBSEC members. Such efforts should be supported by robust, ongoing epidemiological surveillance, with subsequent genomic sequence analysis and pathogenicity studies of both human and animal isolates, to further assess the interconnected risks to animal and public health.