Chest
Volume 139, Issue 4, April 2011, Pages 901-908
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Translating Basic Research into Clinical Practice
Probiotics and Lung Diseases

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Increasing awareness of the role of intestinal commensal bacteria in the development and modulation of the immune system has led to great interest in the therapeutic potential of probiotics and other bacteria-based strategies for a range of immune-related disorders. Studies in animal models have identified strong immunomodulatory effects of many nonpathogenic bacteria and provided evidence that intestinal microbes can activate a common mucosal immune response and, thus, influence sites distant to the intestine, including the respiratory tract. Respiratory effects of probiotics in animal models have included attenuating allergic airway responses and protecting against respiratory pathogens. Dendritic cells appear central to directing the beneficial immune response to probiotic bacteria and in translating microbial signals from the innate to the adaptive immune system, whereas regulatory T cells are emerging as potentially key effectors of probiotic-mediated responses, particularly in the reduction of allergic inflammation. Despite progress in basic research, clinical trials of probiotics in allergy/asthma and respiratory infection have been highly variable at best, leading to an undermining of confidence in this potential therapeutic strategy. It is clear that there is still much to learn regarding the determinants of the diverse immune responses elicited by different bacterial strains. A deeper knowledge of the interactions between administered probiotics and the existing microbiota, together with an understanding of how the dialogue between microbes and the innate immune system is translated into beneficial/protective responses, will be required before we can achieve clinically effective bacteria-based strategies that maintain and promote respiratory health.

Section snippets

Allergy and Asthma

The microflora hypothesis proposes that perturbations in the GI microbiota, because of antibiotic use and dietary differences in industrialized countries, have disrupted the normal microbiota-mediated mechanisms of immunologic tolerance in the mucosa leading to an increase in the incidence of allergic disease, including asthma.1 Proof of principal has been provided in murine models, wherein antibiotic administration causes altered intestinal flora, impaired barrier function, diminished T helper

Tregs: Effectors of the Antiallergic Response?

Diverse populations of Tregs play an important role in regulating Th2 responses to allergen and maintaining functional tolerance. Tregs can be detected at sites of inflammation, and in many situations, their ability to migrate to and remain in inflamed tissue is important for their function in vivo. In rodent asthma models, CD4+CD25+Foxp3+ Tregs are recruited into the lungs and draining lymph nodes and can suppress allergen-induced airway eosinophilia, mucous hypersecretion, and

Dendritic Cells: Key Translators of Microbial Signals

It is an attractive concept that by controlling the maturation and function of dendritic cells (DCs), mucosal immune responses can be modulated. Given that DCs are pivotal in early bacterial recognition and can induce a range of Treg subtypes, there has, understandably, been great interest in interactions between commensal organisms and DCs.

Consequently it is becoming apparent that although Tregs may be major effectors of immune regulation mediated by probiotics, the functional changes in DCs

Probiotics and Lung Infection

The increase in antibiotic resistance and need for new and improved strategies to tackle infectious disease have led to an examination of the therapeutic potential of commensal induced modulation of the mucosal immune response. Consequently, it has been discovered that certain LAB do have protective effects against bacterial and viral infections in the GI and respiratory systems.24 Administration of probiotics has been associated with lower incidence of ventilator-associated pneumonia,25

Challenges to Probiotic-Based Therapies

It is likely that the antiinflammatory efficacy of a probiotic results from a combination of signaling pathways activated as a result of a specific pattern of microbe-derived ligands interacting with the corresponding receptors on host cells (Fig 2). Little is known, however, concerning the nature of the probiotic-host cell interactions, or how these interactions could be manipulated to obtain stronger regulatory responses. Factors to be considered include localization of particular bacteria in

Conclusions

For the reasons outlined previously, the therapeutic efficacy of live probiotic strains may be limited. However, alternative approaches may be developed. To date a number of microbial cell wall components, including polysaccharides50 and lipoteichoic acids,51 as well as potential secreted products,52 have been identified as being critical to the immunoregulatory effects of certain bacteria and/or to mimic the effect of whole organisms, including the ability to attenuate the allergic airway

Acknowledgments

Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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