Streptococcus suis: is nutritional intervention possible?

Streptococcal disease in pigs is an endemic problem caused by Streptococcus suis (S. suis), mostly recognized by neurological clinical signs associated with meningitis, stiff joints, and mortality in the post-weaning phase (Lun et al., 2007; Goyette-Desjardins et al., 2014). The disease is well-associated with tonsil and respiratory tract colonization (Gottschalk and Segura, 2019), although a gastrointestinal infection route is reported as possible (Swildens, 2009). The latter infection route has been debated, however, stomach pH is a strong barrier for S. suis oral models and conditions leading to stomach passage remain to be identified (Warneboldt et al., 2016).

While there is much known about the disease, a repeatable model that mimics a natural infection is still lacking. Quoting Segura et al. (2016), “the initial steps of the pathogenesis of S. suis infection has been a neglected area of research”. Furthermore, S. suis has been persistent in swine production systems for many years and vaccines are still lacking. Autogenous bacterins are the only type used but results are contradictory. Vaccinating piglets from immunized sows is not protective likely due to maternal antibodies inhibitions (Baums et al., 2010). Passive maternal immunity may protect progeny (Rieckmann et al., 2020), but evidence indicates that clearance of S. suis maternal antibodies occurs before weaning regardless of vaccinated or carrier sow origin (Corsault et al., 2021).

If we ask farmers about S. suis incidence, a common answer is “we have few cases every batch and occasionally have outbreaks.” Furthermore, there is an increasing concern that restrictions on antimicrobial use may aggravate the situation. An effort was made to compile field veterinarians’ experiences and published research about the disease risks, which generated a list of empirical questions with evidence. An equation-like hypothesis is proposed to describe a summary of potential factors contributing to reduced or increased disease risk (Figure 1).

Figure 1. Equation-like hypothesis to describe some potential factors contributing to reduced or increased streptococcal disease risk in piglets.

¹It is extensively known that cases and outbreak size range greatly, while prevalence of S. suis virulent strains can still be high.
²Swine influenza increases susceptibility (Meng et al. 2015; Meng et al., 2019) and PRRSv, porcine respiratory circovirus, Bordetella bronchiseptica, S. suis or Haemophilus parasuis can increase incidence of disease, percentage of lungs with lesion, lesions severity, and slower resolution than with a single pathogen infection alone (Segura et al., 2020).
³Caesarean delivered, colostrum deprived pigs are often used for S. suis experimental models (Ferrando et al., 2014; Dekker et al., 2017). Although the level or threshold of colostrum intake needed to influence susceptibility is still unknown.
⁴Some models including stressor factors increased the rate of successful infection model (Swildens et al., 2004; Swildens, 2009; Ferrando et al., 2015).
⁵Hopkins et al. (2019) studied 24 cohort field studies by Cox’s regression and logistic regression where autogenous vaccine effectiveness overall was to be 27% and 21%, respectively. Corsaut et al., (2021), concluded that an autogenous vaccination program for sows and gilts could increase antibodies but maternal immunity did not last enough to protect piglets after weaning. There are only three field experiments available showing efficacy from autogenous bacterins being manufactured by licensed companies (Torremorell et al., 1997; Hopkins et al., 2019; Corsaut et al., 2020).
⁶Exposure to S. suis may be beneficial. A previous low dose challenge with S. suis used to vaccinate pigs, but not previous PRRSV vaccination, resulted in a lower incidence of streptococcal disease in a coinfection model with PRRSv and S. suis (Schmitt et al., 2001). Different S. suis serotype infection or simultaneous co-infection (serotype 2 & 9), can affect mortality and bacterial load; serotype 2 load and mortality were lower in pigs exposed to the two serotypes (Dekker et al., 2017).
⁷Correa-Fiz et al. (2020) reported that medium chain fatty acids combined with a natural anti-inflammatory, showed equivalent results as Amoxicillin to lower prevalence of clinical signs compatible with S. suis.

Without a model to mimic natural infection, it appears obvious that more understanding about host susceptibility and trigger factors for S. suis virulence is still lacking. Authors from above-mentioned recent S. suis research, indicate that the first colonization steps are key. These steps include the pathogen competing with microbiota, resisting local immunity, and finally adhering and crossing the mucosa epithelial barrier. The potential role of mucosa health and immunity, including the interactions between mucosa, biofilm, and S. suis open the field of speculation about feed additives and nutritional interventions. However, we are still lacking solid evidence.

S. suis is highly present in the pig’s oral cavity and transmission occurs across productive phases. Murase et al. (2019), showed that saliva microbiota includes Streptococcus spp. at 16.9% (50.1% S. suis) in suckling piglets, 18.2% (51.8% S. suis) in post-weaning pigs and 9.9% (62.6% S. suis) in sows. Recently, we evaluated 15 piglets from 3 different litters and followed S. suis serotype 9 tonsillar loads over time (Figure 2). Interestingly, 60% of piglets were below the qPCR detection limit before weaning, but all became carriers at day 6 post-weaning. The transmission and/or S. suis load increased post-weaning while 2 naturally diseased pigs, from the same sow but a different pen, were already carriers before weaning. Such results align well with previous findings (Segura et al., 2020).

To date, it is unknown whether reducing carrier rate (transmission), tonsillar load, and gastrointestinal colonization from the suckling phase to the nursery phase may reduce risk of disease, however, it merits further investigation. Oral cavity and mucosa in humans are established as an integral part of general health, including risk of septicaemia diseases and wellbeing (Lockhart et al., 2009; Zawadzki et al., 2016). Some plant extracts and fatty acids have anti streptococcal activity in vitro (Aguiar et al., 2018; Kovanda et al., 2019). In fact, oral hygiene in humans reduced streptococcal disease risk (Okuda et al. 1998, Paju and Scannapieco, 2008; Müller, 2015). Such evidence is hard to demonstrate in pigs, since a natural infection model does not yet exist and must be evaluated in commercial conditions and on a large scale.

Wells et al. (2019) recently reported differences between the tonsillar microbiome of piglets in healthy litters and litters with S. suis cases. Furthermore, Ferrando et al., (2015) demonstrated that low glucose but high glucans in mucosa can trigger S. suis virulence, which is important since glucose is rapidly absorbed but dietary-glucans persist in the oropharyngeal cavity. Looking at the discussion landscape (Figure 1), nutritional factors may become another empirical question contributing to the list, and more research is warranted.

The disease is empirically associated with healthy and heavy piglets, which consume high volumes of sow milk and adapt poorly to solid feed through weaning. They suffer inadequate uptake of nutrients early post-weaning with some villous atrophy, and afterward (3-7 days afterward) abruptly consume large amounts of feed. This contributes to gut tissue damage including inflammation, reduced oxygen supply, increased epithelium permeability and changes in microbiota. Some research indicates that nutritional strategies such as high inclusion of alfalfa lowered S. suis (Zhang et al., 2016) and a different Cu source (hydroxychloride compared to Cu as sulfate 160 mg/kg) lowered Streptococcus spp in the large intestine (Villagómez-Estrada et al., 2020). Recently, Correa-Fiz et al. (2020) reported that medium chain fatty acids combined with a natural anti-inflammatory product showed equivalent results to Amoxicillin to lower the prevalence of clinical signs compatible with S. suis disease compared with lysozyme peptide, MCFA alone, and MFCA plus lysozyme peptide. Furthermore, the MFCA + anti-inflammatory had the highest diversity of nasal microbiota and in turn showed the lowest S. suis disease prevalence. In their trial, sow parity influenced the microbiota composition in both faeces and the nasal passage, which again highlights the importance of a complete approach from the sow to the piglet.

Whether feed additives may be a good alternative to antimicrobials in the current S. suis scenario is still an open question, but recent data warrants more research. The formulation of transversal nutritional programs that manipulate the microbiota and mucosa towards the correct balance should also be incorporated for the S. suis control program.