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      Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

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          Abstract

          The gut-associated microbiota is essential for multiple physiological processes, including immune development. Acquisition of our initial pioneer microbial communities, including the dominant early life genus Bifidobacterium, occurs at a critical period of immune maturation and programming. Bifidobacteria are resident microbiota members throughout our lifetime and have been shown to modulate specific immune cells and pathways. Notably, reductions in this genus have been associated with several diseases, including inflammatory bowel disease. In this review, we provide an overview of bifidobacteria profiles throughout life and how different strains of bifidobacteria have been implicated in immune modulation in disease states. The focus will be examining preclinical models and outcomes from clinical trials on immune-linked chronic conditions. Finally, we highlight some of the important unresolved questions in relation to Bifidobacterium-mediated immune modulation and implications for future directions, trials, and development of new therapies.

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          Diversity of Bifidobacteria within the Infant Gut Microbiota

          Francesca Turroni, Clelia Peano, Daniel A. Pass … (2012)
          Background The human gastrointestinal tract (GIT) represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation. Among the GIT microbiota, bifidobacteria represent an important commensal group, being among the first microbial colonizers of the gut. However, the prevalence and diversity of members of the genus Bifidobacterium in the infant intestinal microbiota has not yet been fully characterized, while some inconsistencies exist in literature regarding the abundance of this genus. Methods/Principal Findings In the current report, we assessed the complexity of the infant intestinal bifidobacterial population by analysis of pyrosequencing data of PCR amplicons derived from two hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected from healthy infants of different geographical origins (Italy, Spain or Ireland), feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean delivery), while in four cases, faecal samples of corresponding mothers were also analyzed. Conclusions In contrast to several previously published culture-independent studies, our analysis revealed a predominance of bifidobacteria in the infant gut as well as a profile of co-occurrence of bifidobacterial species in the infant’s intestine.
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            Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection.

            Saranna Fanning, Lindsay Hall, Michelle Cronin … (2012)
            Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show that Bifidobacterium breve UCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS(+)) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS(+) B. breve reduced colonization levels of the gut pathogen Citrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial-host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts.
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              Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome.

              Peter Whorwell, Linda Altringer, Jorge Morel … (2006)
              Probiotic bacteria exhibit a variety of properties, including immunomodulatory activity, which are unique to a particular strain. Thus, not all species will necessarily have the same therapeutic potential in a particular condition. We have preliminary evidence that Bifidobacterium infantis 35624 may have utility in irritable bowel syndrome (IBS). This study was designed to confirm the efficacy of the probiotic bacteria B. infantis 35624 in a large-scale, multicenter, clinical trial of women with IBS. A second objective of the study was to determine the optimal dosage of probiotic for administration in an encapsulated formulation. After a 2-wk baseline, 362 primary care IBS patients, with any bowel habit subtype, were randomized to either placebo or freeze-dried, encapsulated B. infantis at a dose of 1 x 10(6), 1 x 10(8), or 1 x 10(10), cfu/mL for 4 wk. IBS symptoms were monitored daily and scored on to a 6-point Likert scale with the primary outcome variable being abdominal pain or discomfort. A composite symptom score, the subject's global assessment of IBS symptom relief, and measures of quality of life (using the IBS-QOL instrument) were also recorded. B. infantis 35624 at a dose of 1 x 10(8) cfu was significantly superior to placebo and all other bifidobacterium doses for the primary efficacy variable of abdominal pain as well as the composite score and scores for bloating, bowel dysfunction, incomplete evacuation, straining, and the passage of gas at the end of the 4-wk study. The improvement in global symptom assessment exceeded placebo by more than 20% (p < 0.02). Two other doses of probiotic (1 x 10(6) and 1 x 10(10)) were not significantly different from placebo; of these, the 1 x 10(10) dose was associated with significant formulation problems. No significant adverse events were recorded. B. infantis 35624 is a probiotic that specifically relieves many of the symptoms of IBS. At a dosage level of 1 x 10(8) cfu, it can be delivered by a capsule making it stable, convenient to administer, and amenable to widespread use. The lack of benefits observed with the other dosage levels of the probiotic highlight the need for clinical data in the final dosage form and dose of probiotic before these products should be used in practice.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Top Life Sci
                Journal ID (iso-abbrev): Emerg Top Life Sci
                Journal ID (hwp): ppetls
                Journal ID (publisher-id): ETLS
                Title: Emerging Topics in Life Sciences
                Publisher: Portland Press Ltd.
                ISSN (Print): 2397-8554
                ISSN (Electronic): 2397-8562
                Publication date (Print): 30 November 2017
                Publication date (Electronic): 30 November 2017
                Volume: 1
                Issue: 4 , The Microbiome in Health and Disease
                Pages: 333-349
                Affiliations
                Quadram Institute Bioscience, Norwich Research Park, Norwich, U.K.
                Author notes
                Correspondence: Lindsay J. Hall ( lindsay.hall@ 123456quadram.ac.uk )
                [*]

                These authors contributed equally to this review.

                Article
                Publisher ID: ETLS-1-333
                DOI: 10.1042/ETLS20170058
                PMC ID: 7288987
                PubMed ID: 33525778
                SO-VID: c5dd357c-ca8b-4eb2-aebc-560a965b33d6
                Copyright © © 2017 The Author(s)
                License:

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and the Royal Society of Biology and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                Date received : 23 July 2017
                Date revision received : 22 October 2017
                Date accepted : 25 October 2017
                Categories
                Subject: Aging
                Subject: Host-Microbe Interactions
                Subject: Microbiology
                Subject: Immunology & Inflammation
                Subject: Gastrointestinal, Renal & Hepatic Systems
                Subject: Therapeutics & Molecular Medicine
                Subject: Review Articles

                Keywords: bifidobacterium,immunology,inflammatory bowel disease
                Data availability:
                Keywords: bifidobacterium, immunology, inflammatory bowel disease

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