For the first time, a new study shows that “Probiotics and prebiotics can have different effects on the immune system in male, compared [with] female, piglets.” The findings have important implications for research on the effects of these supplements, as well as for personalized, probiotics-based treatments.
Probiotics are trending in the world of nutrition these days, and a growing body of evidence is suggesting that the hype may well be justified.
Prebiotics, such as the fiber in fruits and vegetables, and probiotics, such as the microorganisms in yogurt and other fermented foods, may keep the whole body healthy by supporting gastrointestinal health and a good balance of bacteria in our guts.
Evidence suggests that probiotics help mediate the host’s immune response, which is why some researchers believe that probiotics may help treat immune-related conditions such as allergies or eczema.
But immunity differs considerably by sex; the medical community recognizes sex-based disparities in adults’ immune responses to various inflammatory and infectious diseases.
However, researchers know less about immunological sex differences in infants and even less about the effect that dietary supplementation with probiotics may have on the early-life development of the immune system.
So, with this in mind, a team led by Marie Lewis, Ph.D. — a lecturer in gut immunology and microbiology at the University of Reading, in the United Kingdom — set out to investigate the effect of pre- and probiotics in young piglets of different sexes.
Lewis and her team published their findings in the journal Frontiers in Immunology.
Sex differences in immune responses
The team used an outbred piglet model to study the potential early sex differences in the immune system. They looked at the immunity in the piglets’ mucosal surfaces, as well as systemic immune responses to new foreign “intruders,” or antigens.
The team found that, at just 28 days old, the piglets showed significant sex-based differences. The immune cells, antibodies, and other immune-related molecules were different in males and females in response to probiotic supplementation.
For instance, males and females responded differently to inulin — a prebiotic derived from the chicory plant. Female pigs produced more of the immunoglobulins IgA and IgM in their lymph tissue, while in male pigs, the process occurred in the large intestine.
Also, “The prebiotic inulin significantly increase[d] the number of cells responsible for controlling immune responses, the regulatory T cells, in male guts but not in female guts,” reports Lewis.
“This suggests that, during infancy, females may have greater potential for local immune regulation than their male counterparts,” write the authors.
Furthermore, they report, “Starch supplementation had no effect on females but increased IgM synthesis in all tissues in males.”
Also, the marker E-cadherin, which can indicate intestinal barrier health, was higher in female piglets fed with inulin.
Finally, female piglets also had “significantly greater systemic antibody responses to injected ovalbumin and dietary soya.”
Surprising results in female piglets
The study shows, “for the first time, that probiotics and prebiotics can have different effects on the immune system in male, compared [with] female, piglets,” says the lead investigator.
She goes on to contextualize the findings, saying, “Correct development of the immune system is essential in ensuring it responds appropriately to both harmful and harmless stimulation throughout life — and this development, even during the first days of life, depends on your sex.”
“Although we don’t know why, we know that young girls tend to produce a more protective immune response to vaccination than boys.”
“But what we did not expect to find is that young girls also appear to have a more regulated immune environment in their intestinal tissues than boys.”
“This is important because around 70% of the immune system is in the gut, and this is also where its development is driven during early life, largely by the resident gut bacteria.”
Marie Lewis, Ph.D.
Implications for treatment, future research
Lewis also explains that the consequences of the findings are twofold. On the one hand, the new study may help explain why previous research on the effectiveness of pre- and probiotic supplementation may have yielded mixed or inconclusive results.
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“We need to rethink how we design and analyze the data from nutritional trials in youngsters,” says Lewis. “Currently, studies looking at the effectiveness of dietary supplements on the immune system assume that the same thing happens in boys and girls.”
“But [in our study,] we show this is not the case and that sex may be influencing data on the effectiveness of probiotics and prebiotics in infanthood.”
The second implication further lends credence to the benefits of personalized medicine. “In the future, we could find that specific probiotics or prebiotics are more beneficial for girls, whilst others could generate better health outcomes for boys,” says Lewis.
“Treatments for immune disorders may need to be designed differently for infant girls and boys.”
Marie Lewis, Ph.D.
“Given the underlying differences in immune development we identified between boys and girls,” Lewis adds, “taking sex into account could provide a simple means to improve the effectiveness of pharmaceutics and other therapies which act on the immune system.”