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Review
. 2014 Aug 29;13 Suppl 1(Suppl 1):S7.
doi: 10.1186/1475-2859-13-S1-S7. Epub 2014 Aug 29.

Towards a better understanding of Lactobacillus rhamnosus GG--host interactions

Marijke E Segers, Sarah Lebeer
Review

Towards a better understanding of Lactobacillus rhamnosus GG--host interactions

Marijke E Segers et al. Microb Cell Fact. .

Abstract

Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions, the results are not univocal. Clearly, the host phenotype governed by age, genetics and environmental factors such as the endogenous microbiota, plays a role in whether individuals are responders or non-responders. However, we believe that a detailed knowledge of the bacterial physiology and the LGG molecules that play a key role in its host-interaction capacity is crucial for a better understanding of its potential health benefits. Molecules that were yet identified as important factors governing host interactions include its adhesive pili or fimbriae, its lipoteichoic acid molecules, its major secreted proteins and its galactose-rich exopolysaccharides, as well as specific DNA motifs. Nevertheless, future studies are needed to correlate specific health effects to these molecular effectors in LGG, and also in other probiotic strains.

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Figures

Figure 1
Figure 1
SpaCBA pili and the molecular mechanisms of adhesion. LGG is very good mucus adhering Lactobacillus strain compared to other probiotic strains such as L. casei Shirota and L. johnsonii LJ1 and the closely related strain L. rhamnosus Lc705. Radioactively labeled bacteria were allowed to adhere to isolated human intestinal mucus. The adhesion ratio (%) was determined by comparing radioactivity of bacteria added to the radioactivity of bound bacteria after washing (A). Data were published before [16]. Presence of SpaCBA pili LGG cells based on a TEM image of LGG labeled with SpaA antiserum and 10 nm protein A gold particles [26] (B) and on a AFM image of LGG in air [37] (C). The predicted model of the pili shows a pilus backbone formed by the major subunit SpaA, as shown in the schematic figure. The minor subunit SpaC is present on the tip and decorates the pilus over the length at ratio 1:2 with SpaA. The Spa B minor pilin serves as a molecular switch for pilus termination and is bound to the peptidoglycan layer. However, it is suggested that leaky activity of the pilin-specific sortase can include SpaB decorations on the pilus (D). Adapted from [26]. The SpaC pilin is thought to serve as a major adhesin of LGG. It can interact with other SpaC molecules, inducing homophilic adhesion, and with intestinal epithelial cells or their extracellular matrix, in heterophilic adhesion. The exact adhesion sites however remain unkown. Pili can have molecular spring properties which makes them capable to withstand shearing stress. Moreover, the SpaC pilin decorated over the pilus length provide a molecular zipper mechanism that can facilitate a close interaction between the host and the bacteria or bacteria with each other (E). Adapted from [35].
Figure 2
Figure 2
Molecular interactions of LGG with intestinal epithelial cells. LTA as a MAMP interacts with TLR2-6, activating NF-κ signaling [43]. Secreted protein Msp2/p40 induces release of HB-EGF that causes phosphorylation of EGF-R, activating downstream protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K) -Akt signaling [51,53,54]. A recent human duodenal transcriptome study indicates that JUN and STAT4 transcription factors play a central role in downstream signaling after consumption of LGG, leading to mainly TH1 cytokine production and activating pathways involved in cellular growth and proliferation, wound healing, angiogenesis, interferon-mediated responses, calcium signaling and ion homeostasis [92]. Adapted from [96]
Figure 3
Figure 3
Pipeline for the design of intervention trials with LGG and related probiotics. In this schema, we have made an overview of different steps that should ideally been taking when designing novel intervention studies with LGG or related probiotics, taking current information into account. For more information, the reader is referred to the main text of this manuscript.
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