Protective Role of Postbiotic Mediators Secreted by Lactobacillus rhamnosus GG Versus Lipopolysaccharide-induced Damage in Human Colonic Smooth Muscle Cells

Cicenia, Alessia; Santangelo, Floriana; Gambardella, Lucrezia; Pallotta, Lucia; Iebba, Valerio; Scirocco, Annunziata; Marignani, Massimo; Tellan, Guglielmo; Carabotti, Marilia; Corazziari, Enrico; Schippa, Serena; Severi, Carola

doi:10.1097/mcg.0000000000000681

Cited by 52 publications

(32 citation statements)

References 29 publications

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“…IBD is a multifactorial immune disorder characterized by chronic inflammation and apoptosis of intestinal cells, which lead to intestinal mucosa damage, oxidative stress, and activation of immune cells with multiple inflammatory mediators ( 48 – 51 ). The soluble factors produced by probiotics, for which the term of “postbiotic” was recently coined, have been reported to alleviate the IBDs ( 22 , 25 , 52 ). Recently, we identified and purified a novel soluble protein from LCS, provisionally named HM0539, and it was found to protect the intestinal barrier ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Yang

Lun

et al. 2020

Front. Immunol.

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Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition with no effective treatment. Probiotics have gained wide attention because of their outstanding advantages in intestinal health issues. In previous studies, a novel soluble protein, HM0539, which is derived from Lactobacillus rhamnosus GG (LGG), showed significant protective effects against murine colitis, but no clear precise mechanism for this effect was provided. In this study, we hypothesized that the protective function of HM0539 might be derived from its modulation of the TLR4/Myd88/NF-κB axis signaling pathway, which is a critical pathway widely involved in the modulation of inflammatory responses. To test this hypothesis, the underlying anti-inflammatory effects and associated mechanisms of HM0539 were determined both in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in dextran sulfate sodium (DSS)-induced murine colitis. Our results showed that HM0539 inhibited the expression of cyclooxygenase-2 (COX-2) and the expression inducible nitric oxide synthase (iNOS) by down-regulating the activation of their respective promoter, and as a result this inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO). Meanwhile, we demonstrated that HM0539 could ultimately modulate the activation of distal NF-κB by reducing the activation of TLR4 and suppressing the transduction of MyD88. However, even though the overexpression of TLR4 or MyD88 obviously reversed the effect of HM0539 on LPS-induced inflammation, HM0539 still retained some anti-inflammatory activity. Consistent with the in vitro findings, we found that HM0539 inhibited to a great extent the production of inflammatory mediators associated with the suppression of the TLR4/Myd88/NF-κB axis activation in colon tissue. In conclusion, HM0539 was shown to be a promising anti-inflammatory agent, at least in part through its down-regulation of the TLR4-MyD88 axis as well as of the downstream MyD88-dependent activated NF-κB signaling, and hence might be considered as a potential therapeutic option for IBD.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Yang

Lun

et al. 2020

Front. Immunol.

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“…Butyrate (a SCFA), was found to support the regeneration of the intestinal epithelium [88]. Meanwhile, supernatant obtained from one of the most common probiotic strains, L. rhamnosus GG, helps to protect human intestinal smooth muscle cells from damage [89]. The use of bacterial lysates in children was associated with significant reduction of respiratory tract infection compared to controls (MD = −2.33; p < 0.00001) [56].…”

Section: Infection Preventionmentioning

confidence: 99%

Postbiotics—A Step Beyond Pre- and Probiotics

et al. 2020

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As an imbalance in the intestinal microbiota can lead to the development of several diseases (e.g., type 1 diabetes, cancer, among others), the use of prebiotics, probiotics, and postbiotics to alter the gut microbiome has attracted recent interest. Postbiotics include any substance released by or produced through the metabolic activity of the microorganism, which exerts a beneficial effect on the host, directly or indirectly. As postbiotics do not contain live microorganisms, the risks associated with their intake are minimized. Here, we provided a critical review of postbiotics described in the literature, including their mechanisms of action, clinical characteristics, and potential therapeutic applications. We detailed the pleiotropic effects of postbiotics, including their immunomodulatory, anti-inflammatory, antioxidant, and anti-cancer properties. Although the use of postbiotics is an attractive strategy for altering the microbiome, further study into its efficacy and safety is warranted.

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“…Blood parameters that have been found to be changed by LGG with statistical significance are TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-18. IL-4 and IL-10 are anti-inflammatory, while the others are proinflammatory cytokines (30)(31)(32)(33)(34)(35)(36)(37)(38).…”

Section: Introductionmentioning

confidence: 99%

A Pilot Randomized Control Trial With the Probiotic Strain Lactobacillus rhamnosus GG (LGG) in ADHD: Children and Adolescents Report Better Health-Related Quality of Life

et al. 2020

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Objectives: This double-blind pilot randomized placebo-controlled trial examined the possible effect of the probiotic strain Lactobacillus rhamnosus GG ATCC53103 (LGG) on symptoms of attention-deficit/hyperactivity disorder (ADHD), health-related quality of life (QoL), and serum levels of cytokines in children and adolescents with ADHD.Methods: This trial evaluated 32 drug-naive children and adolescents aged between four and 17 years with a diagnosis of ADHD. The study subjects were randomly assigned to either the group that received LGG or the group that received the placebo.Report Form (TRF) of the Child Behavior Checklist (CBCL) for ages 6-18 of the Achenbach System of Empirically Based Assessment (ASEBA); and the serum cytokines;were compared between the groups at the baseline and after 3 months.Results: Thirty-five participants were randomized, with 32 completing the study (91.4% retention). There was a significant improvement in the PedsQL Child Self-Report Total Score after 3 months of treatment in the probiotic (p = 0.021, d = 0.53), whereas there was no significant improvement in the placebo group (p = 0.563, d = 0.04). The results of psychometric parameters assessed by parents and teachers were not so straightforward. There were statistically significant differences in the levels of serum cytokines between the groups after the 3-month treatment period: IL-6 in both the probiotic (p = 0.004, d = 0.73) and the placebo groups (p = 0.035, d = 0.94); IL-10 (p = 0.035, d = 0.6); IL-12 p70 (p = 0.025, d = 0.89); and TNF-α (p = 0.046, d = 0.64) in the probiotic group only. Conclusions:Children and adolescents with ADHD who received LGG supplementation reported better health-related QoL compared to their peers who received the placebo. This suggests that LGG supplementation could be beneficial. But results with psychometric tests conducted by parents and teachers as well as differences in the levels of inflammatory cytokines were ambiguous. Based on these Kumperscak et al. Effect of ProbioticLGG in ADHD results, we propose some study modifications: a longer observation period (6-12 months); inclusion of more children's self-report assessments; recruitment of non-drug naive patients and the possible omission of serum cytokines measurements.

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Protective Role of Postbiotic Mediators Secreted by Lactobacillus rhamnosus GG Versus Lipopolysaccharide-induced Damage in Human Colonic Smooth Muscle Cells

Abstract: LGG-derived products are able to protect human SMCs from LPS-induced myogenic damage. Novel insights have been provided for the possibility that LGG-derived products could reduce the risk of progression to postinfective motor disorders.

Cited by 52 publications

References 29 publications

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis

Postbiotics—A Step Beyond Pre- and Probiotics

A Pilot Randomized Control Trial With the Probiotic Strain Lactobacillus rhamnosus GG (LGG) in ADHD: Children and Adolescents Report Better Health-Related Quality of Life

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