Trends in Microbiology
Does the microbiota regulate immune responses outside the gut?
Section snippets
The normal microbiota: characterization and development
The process of colonization of the GI tract after birth leads to a series of ecological successions with the end result being the establishment of a stable microbiota (‘microflora’) that is unique to each individual. The stable adult microbiota is composed of autochthonous species (permanent members) and allochthonous species (transient colonizers that are briefly acquired from an external origin). The adult microbiota is composed of 400–1000 species, with as many as 60% that are not culturable
Altering the microbiota
Environmental pressures, such as antibiotics, diet and microbial inoculation, can cause alterations in an otherwise stable microbiota, both transient and permanent (Box 1). Those microbes that produce only beneficial effects for the host are termed ‘probiotic’ species and include Lactobacillus and Bifidobacterium spp. (Box 3). In addition, potentially pathogenic organisms (PPO) make up part of the microbiota and include the aerobic enteric bacteria, Clostridium spp. and Candida albicans (Box 2
The epidemiological connection between altered microbiota and allergies
Antibiotics, diet and infant-feeding regimens are all associated with the development of allergies and asthma [1]. All three of these also have profound effects on microbiota composition (Box 2). Until recently, the evidence to support a role for the microbiota in allergic disease was based on epidemiological studies as opposed to direct testing of this idea. Numerous studies indicate that the composition of the GI microbiota is different in atopic versus non-atopic individuals and in
The immunological consequences of altered microbiota
It has been known for several years that alterations in the GI microbiota can influence mucosal immunity [10]. Germ-free animals have smaller Peyer's patches, fewer intraepithelial lymphocytes, and lower levels of secretory IgA. In the context of allergic responses, germ-free animals are resistant to the induction of oral tolerance that can block IgE production 20, 21. Inoculation of germ-free mice with intestinal bacteria (conventionalization) can restore the ability to generate oral tolerance.
Role of altered microbiota in allergic airway disease
It has been proposed that the lung microenvironment is generally predisposed to Th2 responses [27]. However, repeated intranasal antigen exposure in the lungs leads to decreasing reactivity, a form of tolerance 28, 29. Oral tolerance is mediated by regulatory T-cell responses, which can down-modulate Th2 responses to the same antigens at sites throughout the body, including the lungs 30, 31, 32. Oral tolerance cannot be generated in germ-free mice, indicating that the GI microbiota plays an
Can the microbiota be manipulated to alter allergic responses?
Numerous studies have indicated that probiotic and prebiotic supplementation (Box 3) can produce positive results in both therapeutic and preventative ways [41]. Although the majority of human trials have focused on the benefits of probiotics in GI diseases (reviewed in Ref. [42]), there is some evidence to suggest that probiotic supplementation can alleviate and/or prevent development of allergic disease. Human trials have targeted neonatal or infant subjects who are at risk (one or more
Is the microbiota a major regulator of the immune system?
For a century, science has known that diet can dramatically alter the microbial composition of the microbiota. For decades, science has been able to demonstrate in animal models the importance of the microbiota for the development and maintenance of the immune system. However, the impact of these findings on human health has not become apparent until the past 20–40 years. During this period of time, powerful forces have been introduced into everyday society that can significantly alter the
Acknowledgements
This work was supported by a New Investigator Award in Molecular Pathogenic Mycology from the Burroughs-Wellcome Fund (Gary B. Huffnagle). Mairi C. Noverr was supported by NIH-NHLBI training grant 2T32HL007749–11. Additional support was provided by to Gary B. Huffnagle by the following grants from the National Institutes of Health: RO1-HL65912, RO1-AI59201.
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