Can Probiotics Help With Autoimmune Disorders?

Autoimmune disorders have been classified as rheumatic, connective tissue, and systemic autoimmune diseases.

Connective tissue diseases include systemic lupus erythematosus (SLE), Sjogren’s syndrome, scleroderma, polymyositis-dermatomyositis; systemic autoimmune diseases are a group of disorders that occur when the immune system attacks organs and tissues normally viewed as “self.”

Autoimmune disorders listed

The list includes rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (DM), and inflammatory bowel disease (IBD). There is increasing evidence supporting that chronic inflammation may be implicated in all these conditions ^[1–4].

The involvement of infectious agents — specifically viruses — in the pathogenesis of some autoimmune diseases has been widely described ^[5,6]. In this context, it is important to mention that chronic infection with the hepatitis C virus (HCV) may also trigger a number of autoimmune disorders including multiple sclerosis, psoriasis, and Sjögren’s syndrome ^[7–10].

The concept that an infectious agent may be linked to the inflammatory process in autoimmunity is not new.

The idea was based on experimental models using animal models such as the “collagen-induced arthritis”, which faithfully reproduced rheumatoid arthritis in humans; however, at present no clear-cut evidence exists regarding an association between acute or persistent viral infections and rheumatoid arthritis.

However, a specific strain of Chlamydia pneumoniae was proven to be associated with increased susceptibility to rheumatoid arthritis and other autoimmune disorders ^[11–13].

The possible etiological role of microorganisms, especially viruses and bacteria in the pathogenesis of inflammatory bowel disease has also been recently reviewed ^[14,15]. Although there is evidence suggesting that some infectious agents may predispose a person to autoimmunity-inducing inflammation and it has been proposed that this would represent one of the molecular mechanisms involved in breaking immunological tolerance, further research is needed for understanding whether different infections could have a role in these diseases.

As mentioned above, a high prevalence of HCV infection has been observed among SLE patients; similarly, it appears that a significant proportion (5-20%) of patients with Sjogren’s syndrome are infected by certain viruses such as Epstein-Barr virus (EBV), hepatitis B or C and cytomegalovirus (CMV) ^[16–19].

According to these results, HCV appears to be in the leading position among known chronic viral infections associated with autoimmune diseases.

In addition, a significant relationship between high levels of HCV antibodies and increased risk for the development of DM has been described in some studies; this was independent of any evidence that diabetes was directly caused by HCV infection itself ^[20].

In addition, an association between MS and mycobacterial infections has also been observed.

Other infectious agents like EBV, Toxoplasma gondii, enteroviruses, or Helicobacter pylori have been proposed to be associated with the development of MS ^[21–24].

However, in contrast to these findings, some other studies failed to verify any link between HCV infection and autoimmune rheumatic disease.

For example, an Italian study found HCV seropositivity in 5% of SLE patients compared with 9% among controls (p = 0.3), while another study from France reported no evidence that Sjogren’s syndrome was associated with HCV infection ^[25–27].

Sesay et al recently concluded a systematic review and meta-analysis of published studies examining associations between infectious agents including hepatitis viruses and multiple sclerosis (MS) as well as other related autoimmune diseases.

The authors suggested that infection may play a role in the pathogenesis of MS and they proposed that this may be explained by molecular mimicry ^[28].

Also, there is evidence suggesting that HCV might play an important role in the development of IBD; however, its precise effect on susceptibility to IBD remains unclear, since data are conflicting. In some studies, no association was observed between chronic hepatitis C infection and risk for Crohn’s disease (CD) while a weak association was found with ulcerative colitis (UC).

On the other hand, HRs were reported to vary according to gender and genetic background: women may have up to three times higher risk of developing CD than men who instead run higher risks for UC ^[29].

In another study of German patients with chronic HCV infection, where the prevalence of IBD was compared with that observed in the general population, no association between these two diseases was found.

However, there was a significant increase in risk for CD in patients who were non-smokers and/or had liver cirrhosis ^[30].

Particularly intriguing is the evidence suggesting that exposure to either HCV or HBV might be associated with several cognitive deficits including depression.

In fact, some authors suggest that it could play an important role in predisposing to Alzheimer’s disease (AD) because of its neurotropic properties which can induce neuroinflammation characterized by activation of microglia and astrocytes induction ^[31,32].

Further evidence of the role of chronic viral infections in IBD pathogenesis comes from findings that HCV-positive patients with IBD have a more aggressive disease than HCV-negative patients.

The rate of complications for CD is also higher in patients infected by HBV or HCV compared to noninfected CD and UC patients ^[33], consequently suggesting that chronic hepatitis virus infection could play a role in the development of an immune dysregulation driving towards autoimmunity against intestinal antigens ^[34].

Recent studies have begun to investigate the relationship between autoimmune diseases such as SLE and lupus nephritis (LN) and infectious agents including mold toxins, EBV, and different herpesviruses (HHV6,7,8), Chlamydia pneumoniae and Ureaplasma urealyticum.

However, no consistent evidence could be found ^[35–37].

As for SLE, there are also some data suggesting a link between hepatitis C infection (HCV) with primary biliary cirrhosis (PBC).

In fact, some researchers suggest that this association can be explained by the molecular mimicry theory. According to this hypothesis, HCV antibodies crossreact with epitopes of misfolded proteins such as PBC anti-mitochondrial antibodies ^[38].

Further studies into autoimmune disorders

Further studies confirming these results should be conducted in order to verify whether the relationship observed between hepatitis viruses and autoimmune diseases is casual or not.

Meanwhile few papers discussed the possible beneficial effect of probiotics in autoimmune diseases such as MS, ADHD, and inflammatory bowel disease (IBD). Suez et al conducted a randomized trial evaluating the effects of a probiotic formulation (Lactobacillus casei) on IBD in children with autism spectrum disorders.

Thirty-three children aged 6–18 years received either placebo or a probiotic preparation for 4 weeks; those receiving the probiotic had significantly higher mean defecation frequency/day than the control group ^[39].

Also, Gonda et al suggested that Lactobacillus paracasei NCC2461 has an anti-inflammatory property even when administered transiently.

The authors tested its effect on TNFα production by murine peritoneal macrophages by administering 1×10^8 or 5×10^8 CFU of viable cells.

The authors observed that both doses significantly reduced TNFα production (33 and 44% respectively). Based on these data the authors suggested that Lactobacillus paracasei could be a useful treatment for inflammatory bowel disease without inducing antibiotic-associated side effects ^[40].

In conclusion, in spite of strong evidence supporting the causal role of genetic factors in IBD susceptibility, it is evident that environmental factors are also fundamental players in IBD onset and progression.

Among these triggers, there are infectious agents which can be very difficult to eliminate.

However, preventing exposure to environmental triggers or decreasing their damaging effect should open new therapeutic strategies for immune-mediated diseases.

In fact, some authors suggest that dietary interventions may play a major role in preventing inflammatory bowel disease ^[41].

The impact of diet on the intestinal microflora already attracted early interest with respect to the association between yogurt consumption and protection from CD ^[42].

Nevertheless, this hypothesis needed further evidence, currently suggested by literature reviews concluding that probiotics could represent a novel class of therapeutic agents in inflammatory bowel disease ^[43,44].

These findings suggest that the intestinal microflora could also represent an alternative therapeutic target for autoimmune diseases.

Probiotics can reach the intestine in different ways including food and dietary supplements but also intravenously, intranasally, or topically (skin).

In fact, there are data supporting their use as adjuvant therapy in certain conditions such as transplantation ^[45], antibiotic-associated diarrhea, or irritable bowel syndrome ^[46] while some studies have reported negative results ^[47,48].

In conclusion

These considerations lead us to think about probiotics as a possible treatment for immune-mediated diseases but especially to consider them as a preventive measure against environmental triggers which may be responsible for the onset of these diseases and which could be removed, at least in part, by these approaches.

A number of prebiotic oligosaccharides can also modulate the immune response. These compounds have a selective stimulatory activity for bifidobacteria, which selectively increases in the gastrointestinal tract.

In particular, galactooligosaccharides can modulate intestinal transport processes and reduce gut inflammation ^[49].

The authors conclude that probiotics and prebiotics may represent real alternatives to antibiotics by controlling microbial colonization of the small intestine while maintaining their beneficial effects on digestion throughout the gastrointestinal tract.

Moreover could be an attractive therapeutic approach to maintaining intestinal homeostasis and preventing immune-mediated disease onset.

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