Effect of <i>Lacticaseibacillus paracasei</i> strain Shirota supplementation on clinical responses and gut microbiome in Parkinson's disease

Yang, Xiaodong; He, Xiaoqin; Xu, S. B.; Zhang, Yi; Mo, Chengjun; Lai, Yiqiu; Song, Yanyan; Yan, Zheng; Ai, Penghui; Qian, Yiwei; Xiao, Qin

doi:10.1039/d3fo00728f

Cited by 25 publications

(14 citation statements)

References 44 publications

(49 reference statements)

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“…However, more identified RNA transcripts exhibited a stronger association with the short PFS patient group, namely, 92% (35 out of 38) with a minimum AUC of 7.0. Among them, alkaline, reducing fluidresident Hakubanella thermoalkaliphilus from the Actinomycetota phylum [65] was not yet described in connection with the human microbiome, whereas the genus Lacticaseibacillus, along with other Lactobacillus species described as lactic acid producer probiotics were already heavily implicated in gut health and immunity, including alleviating GI symptoms in Parkinson's disease [66], contribution to cell-wall remodeling and gut microbiome homeostasis [67]. In cancer, the genus has been assigned an anti-proliferative role boosting anti-tumor immunity, but only in colorectal cancer and mouse models [68,69].…”

Section: Discussionmentioning

confidence: 99%

Gut Metatranscriptomics Based De Novo Assembly Reveals Microbial Signatures Predicting Immunotherapy outcomes in Non-Small Cell Lung Cancer

Dora,

Kiraly,

Somodi

et al. 2024

Preprint

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Background: Advanced-stage non-small cell lung cancer (NSCLC), presents significant treatment challenges, with immune checkpoint inhibitor (ICI) combinations being the primary therapeutic option. Emerging evidence highlights the gut microbiome's pivotal role in modulating the efficacy of such immunotherapies. Our study aims to elucidate the association between the gut microbiome and ICI treatment outcomes in NSCLC patients, focusing on identifying metatranscriptomic (MTR) signatures predictive of therapy response. Methods: Utilizing a De Novo Assembly-based MTR analysis on fecal samples from 29 NSCLC patients undergoing ICI therapy, the study segmented patients based on progression-free survival (PFS) into long (>6 months) and short (≤6 months) PFS groups. Through RNA sequencing, we employed the Trinity pipeline for assembly, MMSeqs2 for taxonomic classification, DESeq2 for differential expression (DE) analysis. We constructed Random Forest (RF) and Support Vector Machine (SVM) machine learning algorithms and comprehensive microbial profiles. Results: There were significant microbial composition variances between the two PFS groups. Notably, Actinomycetota was significantly overrepresented in patients with short PFS (vs long PFS, 36.7% vs. 5.4%, p<0.001), as was Euryarchaeota (1.3% vs. 0.002%, p=0.009), while Bacillota showed higher prevalence in the long PFS group (vs short PFS, 66.2% vs. 42.3%, p=0.007). Among the 120 significant DEGs identified, cluster analysis clearly separated a large set of gene clusters more active in patients with short PFS and a smaller set of genes more active in long PFS patients. RF and SVM machine learning models confirmed the predictive validity of the microbial signatures, with ROC AUCs of 0.878 and 0.85, respectively. Furthermore, multivariate analyses incorporating clinical variables such as PD-L1 expression and chemotherapy history underscored the influence of n=6 RNA-based microbial biomarkers on PFS. Conclusion: Using ML models, specific gut microbiome MTR signatures' associate with ICI treated NSCLC outcomes. Expression of specific gene clusters and microbial taxonomy might differentiate long vs short PFS.

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Section: Discussionmentioning

confidence: 99%

Gut Metatranscriptomics Based De Novo Assembly Reveals Microbial Signatures Predicting Immunotherapy outcomes in Non-Small Cell Lung Cancer

Dora,

Kiraly,

Somodi

et al. 2024

Preprint

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“…Probiotics are live microorganisms that, when ingested in appropriate amounts, positively affect resident intestinal microbiota and improve the symptomatology of a wide range of chronic diseases, especially GIT ones [48][49][50]. Preliminary human studies have shown improvements in intestinal symptoms [51][52][53], depression [54], and motor and metabolic markers [55]. Murine data support their anti-inflammatory potential in PD therapy [23,56].…”

Section: Non-dietary Gut Microbiota-targeted Interventionsmentioning

confidence: 98%

The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson’s Disease Animal Models—A Systematic Review

Panaitescu,

Răzniceanu,

Mocrei-Rebrean

et al. 2024

CIMB

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Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson’s disease by rebalancing the gut microbiome in the context of the gut–brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson’s disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson’s disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.

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“…Emerging research posits that pathogenic variants of alpha-synuclein—a hallmark protein in PD—may originate within the gut and ascend to the brain through the vagus nerve, implicating this route in the disease’s early development and progression ( 13 , 22 , 32 , 41 , 46 , 49 , 58–60 ). Additionally, the gut microbiota’s role in neurotransmitter production, such as serotonin and dopamine, which are integral to mood regulation and motor control, respectively, further underscores its potential impact on PD symptomatology ( 13 , 20 , 21 , 25 , 31 , 32 , 35 , 38 , 39 , 42 , 43 , 45 , 48 , 50 , 53 , 61 ).…”

Section: Mechanisms Of Gut Microbiota Influence On Pdmentioning

confidence: 99%

“…In PD, alterations in the production of gut microbiota-derived metabolites may compromise neuronal health and foster neurodegeneration ( 19 , 20 , 22 , 24–26 , 28 , 30–32 , 35–44 , 46–54 , 56–61 ). The microbiota’s capacity to regulate the secretion of gut hormones such as ghrelin and glucagon-like peptide-1 (GLP-1), both noted for their neuroprotective properties, may also be pivotal in modulating PD’s progression ( 23 , 27 , 31 , 33 , 35 , 39 , 53 ).…”

Section: Mechanisms Of Gut Microbiota Influence On Pdmentioning

confidence: 99%

“…Such systemic inflammation is believed to intensify neuroinflammation, thereby exacerbating PD’s neurodegenerative trajectory ( 13 , 21–23 , 27 , 28 , 32 , 34–36 , 39 , 41 , 44 , 46–48 , 50 , 52–54 , 56–60 ). Notably, certain gut bacterial strains are known to induce regulatory T cells (Tregs) production, pivotal in dampening inflammatory responses ( 21 , 23 , 27 , 32 , 35 , 39 , 53 ). A disruption in this delicate balance within the gut microbiota may undermine these regulatory mechanisms, propelling unchecked inflammation ( 21 , 23 , 27 , 32 , 35 , 39 , 53 ).…”

Section: Mechanisms Of Gut Microbiota Influence On Pdmentioning

confidence: 99%

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The interplay between gut microbiota and the brain-gut axis in Parkinson’s disease treatment

Jia,

Wang,

Liu

et al. 2024

Front. Neurol.

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This study delves into the pivotal role of the gut microbiota and the brain-gut axis in Parkinson’s Disease (PD), a neurodegenerative disorder with significant motor and non-motor implications. It posits that disruptions in gut microbiota—dysbiosis—and alterations in the brain-gut axis contribute to PD’s pathogenesis. Our findings highlight the potential of the gastrointestinal system’s early involvement in PD, suggested by the precedence of gastrointestinal symptoms before motor symptoms emerge. This observation implies a possible gut-originated disease pathway. The analysis demonstrates that dysbiosis in PD patients leads to increased intestinal permeability and systemic inflammation, which in turn exacerbates neuroinflammation and neurodegeneration. Such insights into the interaction between gut microbiota and the brain-gut axis not only elucidate PD’s underlying mechanisms but also pave the way for novel therapeutic interventions. We propose targeted treatment strategies, including dietary modifications and fecal microbiota transplantation, aimed at modulating the gut microbiota. These approaches hold promise for augmenting current PD treatment modalities by alleviating both motor and non-motor symptoms, thereby potentially improving patient quality of life. This research underscores the significance of the gut microbiota in the progression and treatment of PD, advocating for an integrated, multidisciplinary approach to develop personalized, efficacious management strategies for PD patients, combining insights from neurology, microbiology, and nutritional science.

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Effect of Lacticaseibacillus paracasei strain Shirota supplementation on clinical responses and gut microbiome in Parkinson's disease

Abstract: Parkinson’s disease (PD) is a common neurodegenerative disease characterized by motor issues and a range of nonmotor symptoms. Microbial therapy may be a useful approach for the treatment of PD....

Cited by 25 publications

References 44 publications

Gut Metatranscriptomics Based De Novo Assembly Reveals Microbial Signatures Predicting Immunotherapy outcomes in Non-Small Cell Lung Cancer

Gut Metatranscriptomics Based De Novo Assembly Reveals Microbial Signatures Predicting Immunotherapy outcomes in Non-Small Cell Lung Cancer

The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson’s Disease Animal Models—A Systematic Review

The interplay between gut microbiota and the brain-gut axis in Parkinson’s disease treatment

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