Effects of probiotics on markers of immunity and inflammation in the elderly

Abstract

Human life span is increasing steadily. Between 1970 and 2016 global life expectancy rose by an average of 13.5 years for men and 14.8 years for women. Although this is the result of better interventions and preventative strategies, the immune system undergoes fundamental changes throughout the ageing process. Some aspects of innate and acquired immunity decline, termed immunosenescence, while low grade inflammation emerges, termed inflammageing. Together, these make older people more susceptible to infections, poor responses to vaccinations and to many chronic conditions. Ageing also results in changes in the gut microbiota, which plays a role in controlling host immune and inflammatory responses. Conversely, the host immune system has a role in controlling the microbiota. Age-related changes in immunity, inflammation and gut microbiota may be linked. Probiotics are microorganisms, usually bacteria, which are reported to confer health benefits on the host. They act through interaction with the existing microbiota, the gut-associated immune system, and enterocytes. The effect of probiotics on immune function and markers of inflammation have not been well explored in elderly care home residents (ECHRs). In order to prepare for analyses conducted as part of a trial investigating a probiotic intervention in ECHRs, a pilot study investigating the effect of blood storage time on a range of immune and inflammatory biomarkers was conducted. It was identified that some markers need to be measured using fresh blood while others can be measured in blood stored for up to 24 hours, or in some cases for longer. Subsequently, blood samples from a subset of subjects enrolled in a placebo-controlled trial of the combination of two probiotic organisms (Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. BB-12) in ECHRs were used to investigate the effects of the probiotics on a range of markers of innate and acquired immunity, low grade inflammation and the response to seasonal influenza vaccination. None of these markers was significantly affected by the probiotic intervention. Using samples obtained at study entry, it was identified that frailty and age were associated with some markers of low-grade inflammation. In addition to this mechanistical exploration, the In vitro epithelial cell line Caco-2 was used as a model of the human epithelial gut to investigate the effects of LGG and BB-12 on barrier function and inflammation. Neither live nor heat-inactivated LGG or BB-12 themselves induced an inflammatory response. Transepithelial Electrical Resistance (TEER) tend to increase more when the live version was used when compared with the heat-inactivated version. Lastly, the exposure to either organism (heat-inactivated) for 24 hours prior to stimulation with an inflammatory cocktail reduced the inflammatory response (assessed by measuring cytokines in the culture medium). LGG and BB-12 were equally effective, however, heat-inactivated organisms did not affect the loss of barrier function caused by the inflammatory cocktail. Research conducted in this thesis indicates that probiotics strains LGG or BB-12 did not influenced immune parameters in ECHRs, whilst the in vitro evidence suggest a possible “local” effect exerted by these strains on epithelial cells. Overall, this area warrants further research throughout a wider exploration of the heterogeneity of the ageing process. Studying different degrees of frailty, and environments is paramount. Likewise, more evidence is required to link localized effects exerted on epithelial cells. Adding an understanding of surrounding cells interacting
with gut epithelia will allow to progress the understanding of systemic effects from a local
perspective.

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Identifiers

ORCID for Philip Calder: orcid.org/0000-0002-6038-710X

ORCID for Elizabeth Miles: orcid.org/0000-0002-8643-0655

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