Long-term intake of Lactobacillus paracasei KW3110 prevents age-related chronic inflammation and retinal cell loss in physiologically aged mice

Morita, Yuji; Jounai, Kenta; Sakamoto, Akihiko; Tomita, Yasuyuki; Sugihara, Yoshihiko; Suzuki, Hiroaki; Ohshio, Konomi; Otake, Masato; Fujiwara, Daisuke; Kanauchi, Osamu; Maruyama, Mitsuo

doi:10.18632/aging.101583

Cited by 30 publications

(24 citation statements)

References 68 publications

(57 reference statements)

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“…In addition, the authors demonstrated that T-cell activations and glaucomatous neurodegeneration were abolished in GF mice, strengthening the hypothesis that a bacteria-sensitized T-cell responses underly the pathogenesis of glaucoma [237]. In line with these data, long-term intake of Lactobacillus paracasei KW3110 has been associated with a more abundance of beneficial gut bacteria and a reduction of the age-related immune dysfunctions, i.e., lowered expansion of pro-inflammatory T cells and serum cytokines [238]. Instead, this probiotic treatment determined a reduction of the Firmicutes to Bacteroidetes ratio, demonstrated by increased Bifidobacteriaceae and decreased Streptococcaceae families.…”

Section: Human Disease N-3 Pufas and Gut Microbiotamentioning

confidence: 61%

Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System

Parolini

2019

Marine Drugs

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Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids (PUFAs), which are plentiful in fish oil, in different disease states. Mechanisms responsible for the efficacy of n-3 PUFAs include: (1) Reduction of triglyceride levels; (2) anti-arrhythmic and antithrombotic effects, and (3) resolution of inflammatory processes. The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut, and that there has been a significant variability of taxa in the microbiota composition among people. Several factors (gestational age, mode of delivery, diet, sanitation and antibiotic treatment) influence the bacterial community in the human gastrointestinal tract, and among these diet habits play a crucial role. The disturbances in the gut microbiota composition, i.e., gut dysbiosis, have been associated with diseases ranging from localized gastrointestinal disorders to neurologic, respiratory, metabolic, ocular, and cardiovascular illnesses. Many studies have been published about the effects of probiotics and prebiotics on the gut microbiota/microbioma. On the contrary, PUFAs in the gut microbiota have been less well defined. However, experimental studies suggested that gut microbiota, n-3 PUFAs, and host immune cells work together to ensure the intestinal wall integrity. This review discussed current evidence concerning the links among gut microbiota, n-3 PUFAs intake, and human inflammatory disease.

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Section: Human Disease N-3 Pufas and Gut Microbiotamentioning

confidence: 61%

Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System

Parolini

2019

Marine Drugs

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“…Another recent study shows that modifying the gut microbiome by feeding mice L.paracasei KW3110 demonstrates favorable changes in retinal function and morphology on the aging retina. (19) These studies lay the groundwork for the connection between the enteric microbiome and the retina; however, these investigations did not reveal if the microbiota or its metabolites may alter the retinal gene expression. RNA-seq is a revolutionary technique that can generate very precise results to study the entire transcriptome of the tissue.…”

Section: Discussionmentioning

confidence: 99%

High Throughput RNA Sequencing of Germ-Free Mouse Retina Reveals Metabolic Pathways Involved in the Gut-Retina Axis

Nadeem

Xie

Movahedan

et al. 2020

Preprint

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Background and aimsConnections between the gut microbiome and retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), and primary open-angle glaucoma (POAG) are recently being established. Communication between the gut microbiome and retina, referred to as the gut-retina axis, has been proposed; however, the biologic pathways and mediators involved in the interactions have not yet been elucidated. Using high-throughput RNA sequencing (RNA-seq) of whole retinas, we compare the retinal transcriptome from germ-free (GF) and specific pathogen-free (SPF) mice to investigate effects of the gut-microbiome on both retinal gene expression and biologic pathways.MethodsRNA was extracted from whole retinas of GF and SPF mice (four animals per group) and cDNA libraries were created. RNA-seq was performed on NovaSEQ6000 using the paired-end method. After preprocessing the RNA-seq data, gene expression value was calculated by count per million (CPM). The differentially expressed genes (DEGs) were identified with edgeR Bioconductor analysis of expression data. Functional enrichment and protein-protein interaction (PPI) network analyses were created for the differentially expressed genes (DEGs).ResultsRNA-sequencing reveals a cohort of 396 DEGs, of which, 173 are upregulated and 223 are downregulated in GF mouse retina. Enrichment analysis reveals that the DEGs are involved in glucocorticoid effects, transcription factor binding, cytoskeletal stability, lipid metabolism, and mitogen-activated protein kinase (MAPK). Multiple biologic pathways, including obesity/metabolic syndrome, longevity, and 5’ AMP-activated protein kinase (AMPK) signaling pathway are affected in the GF retinas. PPARG1a (PGC1a) gene is involved in 12 of the 16 significantly modulated pathways. Proteins with the most number of interactions in the PPI are E1A binding protein P300(EP300), forkhead box O3(FOXO3) and PGC1a.ConclusionsTo our knowledge, this is the first study demonstrating the involvement of the gut microbiome in driving the retinal transcriptome, providing evidence for the presence of a gut-retina axis. Future studies are needed to define the precise role of the gut-retina axis in the pathogenesis of retinal diseases.

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“…KW3110 was previously reported to activate macrophages by interacting with gut immune cells and promoting cytokine production, including IL-10 [ 10 , 13 , 20 ]. It has also been reported that KW3110 suppresses the level of pro-inflammatory cytokines such as IL-1β in the serum of aged mice or the retina of blue-light exposure-induced mice [ 13 , 14 ]. These results suggest that KW3110 ameliorates IL-1β production in inflammatory-stressed immune cells through the IL-10 signaling pathway in both mice and humans ( Fig 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…KW3110 was shown to activate M2 macrophages with anti-inflammatory reactions, and induce the production of anti-inflammatory cytokine interleukin (IL)-10 [ 13 ]. In addition, KW3110 mitigated aging-related chronic inflammation and blue-light exposure-induced retinal inflammation in mice, at least partially through activating immune cells and reducing pro-inflammatory cytokine production, such as IL-1β [ 13 , 14 ]; however, the mechanism underlying the anti-inflammatory effects of KW3110 remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Lactic acid bacterium, Lactobacillus paracasei KW3110, suppresses inflammatory stress-induced caspase-1 activation by promoting interleukin-10 production in mouse and human immune cells

Yamazaki

Ohshio²,

Sugamata³

et al. 2020

PLoS ONE

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A strain of lactic acid bacteria, Lactobacillus paracasei KW3110 (KW3110), activates M2 macrophages with anti-inflammatory reactions and mitigates aging-related chronic inflammation and blue-light exposure-induced retinal inflammation in mice. However, the mechanism underlying the anti-inflammatory effects of KW3110 remains unclear. In this study, we investigated the anti-inflammatory effects of KW3110 using both mouse and human immune cells and evaluated the suppressive effect of KW3110 on the inflammatory reactions of the cells stimulated with lipopolysaccharide and adenosine 5 0-triphosphate (LPS/ATP). KW3110 treatment induced anti-inflammatory cytokine interleukin (IL)-10 production in the supernatants of murine macrophage-like cells, J774A.1, and suppressed IL-1β production in the supernatants of LPS/ATP-stimulated cells. The influence of KW3110 on the production of these cytokines was inhibited by pre-treatment with phagocytosis blocker or transfection with siRNAs for IL-10 signaling components. KW3110 treatment also suppressed activation of caspase-1, an active component of inflammasome complexes, in LPS/ATPstimulated J774A.1 cells, and its effect was inhibited by transfection with siRNAs for IL-10 signaling components. In addition to the effects of KW3110 on J774A.1 cells, KW3110 treatment induced IL-10 production in the supernatants of human monocytes, and KW3110 or IL-10 treatment suppressed caspase-1 activation and IL-1β production in the supernatants of LPS/ATP-stimulated cells. These results suggest that KW3110 suppresses LPS/ATP stimulation-induced caspase-1 activation and IL-1β production by promoting IL-10 production in mouse and human immune cells. Our findings reveal a novel anti-inflammatory mechanism of LAB and the effect of KW3110 on caspase-1 activation is expected to contribute to constructing future preventive strategies for inflammation-related disorders using food ingredients.

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Long-term intake of Lactobacillus paracasei KW3110 prevents age-related chronic inflammation and retinal cell loss in physiologically aged mice

Cited by 30 publications

References 68 publications

Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System

Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System

High Throughput RNA Sequencing of Germ-Free Mouse Retina Reveals Metabolic Pathways Involved in the Gut-Retina Axis

Lactic acid bacterium, Lactobacillus paracasei KW3110, suppresses inflammatory stress-induced caspase-1 activation by promoting interleukin-10 production in mouse and human immune cells

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