排版丨水成文 代谢功能障碍相关脂肪性肝病 （MASLD） ，此前被称为非酒精性脂肪肝病 （NAFLD） ，正日益受到关注，成为全球 性的健康危机。它涵盖了从单纯脂肪变性到代谢功能障碍相关脂肪性肝炎 （MASH） 的范围，病情可能会发展为肝纤 维化、肝硬化，甚至肝细胞癌。 尽管 MASLD 的负担沉重且其病理生理学复杂，但目前仅有 1 种药物 （瑞美替罗） 获批专门用于 MASH 的治疗，这 凸显了迫切需要更多替代策略，其中 益生元 已崭露头角，成为颇具前景的候选方案。 2025 年 11 月 2 0 日， 上海交通大学医学院附属第六人民医院 李华婷 教授、上海交通大学数学科学学院 / 人工智能 学院 陈洛南 教授、上海交通大学医学院附属第六人民医院 倪岳琼 研究员、上海科技大学 / 上海临床研究中心 曾嵘 教 授及上海交通大学医学院附属第六人民医院 贾伟平 教授等， 在 Cell 子刊 Cell Metabolism 上 发表了题为： Interindividual variability in gut microbiome mediates the efficacy of resistant starch ...

LifeVantage Conference Call Summary Company Overview - **Company Name**: LifeVantage (NasdaqCM: LFVN) - **Industry**: Direct Selling, Nutraceuticals - **Headquarters**: Near Salt Lake City, Utah - **Years in Business**: 16 years - **Active Customers and Consultants**: Approximately 132,000 globally - **Geographic Presence**: Products sold in about 20 countries, with 80% of revenue from North America [2][4] Financial Performance - **Fiscal Year Ended June 30**: - Revenue: $229 million, up 14% year-over-year [3] - EBITDA: Just under $10 million [3] - **Revenue Model**: 70% of revenue is subscription-based, with a 30-day consumption model for products [2][11] - **Balance Sheet**: - Cash: Approximately $20 million - No debt - Working capital: $24 million [15] Product Portfolio - **Core Products**: - Protandim Nrf2: Flagship product, accounts for 50% of revenue, clinically proven to reduce oxidative stress by 40% in 30 days [6] - TrueScience Liquid Collagen: Increases collagen production by 100% [7] - MindBody GLP-1 System: Natural alternative to synthetic drugs, proven to increase GLP-1 production by over 200% [9] - P84 (from LoveBiome acquisition): Focused on gut microbiome [11] - **Market Potential**: - GLP-1 market projected to grow from $19 billion to $88 billion [10] - Gut health market projected to reach $32 billion [11] Strategic Initiatives - **Acquisition**: Acquired LoveBiome to enhance product offerings and geographic reach [5][11] - **Compensation Plan**: Modernized to attract both traditional business builders and micro-influencers, allowing earnings of up to 40% on product sales [12] - **E-commerce Development**: Partnership with Shopify to enhance customer experience [13][17] Growth Opportunities - **Geographic Expansion**: Underrepresented in Europe and Asia, presenting significant growth opportunities [4][20] - **Product Innovation**: Continuous investment in product development and operational efficiencies [14][17] - **Subscription Model**: Provides consistent revenue stream, reducing volatility [20] Shareholder Returns - **Stock Buyback Program**: $60 million plan, with $17 million remaining for future repurchases [18] - **Dividends**: Regular increases in dividend payouts since introduction [19] Market Positioning - **Health Conscious Consumer Base**: Products cater to a growing trend of proactive health management [19][20] - **Competitive Advantage**: Strong foundation with patented, science-backed products supported by clinical studies [22] Conclusion - LifeVantage is positioned for sustained growth through strategic acquisitions, product innovation, and a strong subscription model, while also focusing on expanding its international presence and enhancing its compensation plan to attract new sales representatives [20][22]

Core Insights - The study indicates that gut microbiota can predict the efficacy of consolidation immunotherapy and chemoradiotherapy toxicity in lung cancer patients [3][9] - The research highlights the dynamic changes in gut microbiota during treatment and its correlation with progression-free survival (PFS) and treatment-related lung toxicity [5][6] Group 1: Research Findings - The research team utilized 16S rRNA sequencing to track the dynamic changes in gut microbiota of stage III lung cancer patients undergoing concurrent chemoradiotherapy (CRT) and consolidation immune checkpoint inhibitors (ICI) [5] - In traditional CRT, the composition of gut microbiota remained unaffected, whereas in CRT combined with ICI, patients with longer PFS exhibited higher baseline gut microbiota diversity, which decreased during treatment [6][9] - The abundance of Akkermansia muciniphila (Akk) increased post-chemoradiotherapy, correlating with extended distant metastasis-free survival in patients receiving CRT combined with ICI [6][10] Group 2: Clinical Implications - The study suggests that the overall clinical benefit of CRT combined with ICI is significantly greater compared to CRT alone for locally advanced lung cancer patients [9] - The dynamic changes in Akkermansia muciniphila serve as a potential prognostic indicator for patient survival outcomes [10] - Distinct gut microbiota characteristics were observed in patients who developed severe lung toxicity post-treatment, indicating a possible predictive marker for treatment-related pneumonia [6][10]

Core Insights - A recent study presented at UEG Week 2025 indicates that microplastics alter the human gut microbiome, with changes resembling patterns associated with depression and colorectal cancer [1][2] - This research is among the first to directly examine how different types of microplastics interact with the human gut microbiome [1] Summary by Sections Study Methodology - The study utilized fecal samples from five healthy volunteers for in vitro gut microbiome cultivation, exposing these cultures to five common types of microplastics: polystyrene, polypropylene, low-density polyethylene, polymethyl methacrylate, and polyethylene terephthalate [1] - Concentrations of microplastics reflected estimated human exposure levels, with higher doses used to investigate potential dose-dependent effects [1] Findings on Bacterial Composition - While total bacterial cell counts and viable bacterial cell counts remained largely unchanged, the acidity of the microplastic-treated cultures significantly increased compared to the control group, indicating altered microbial metabolic activity [1] - Specific changes in bacterial composition were observed, with certain bacterial populations increasing or decreasing depending on the type of microplastic, particularly within the phylum Firmicutes, which is crucial for digestion and overall gut health [1] Chemical Changes and Disease Implications - Changes in the chemical substances produced by bacteria accompanied the shifts in bacterial composition, with some correlating with the observed increase in acidity [2] - Certain types of microplastics altered levels of pentanoic acid and 5-aminopentanoic acid, while others affected lysine or lactic acid, highlighting the complexity of microplastic-microbiome interactions [2] - Notably, some of the microbially induced changes reflect patterns previously associated with diseases such as depression and colorectal cancer, underscoring the potential health risks linked to microplastic exposure [2]

Core Insights - The gut microbiome is a significant predictor of health, influencing metabolism, weight, brain health, and aging [3][4] - Dysbiosis, or an imbalance in gut microbes, is linked to various chronic diseases, including obesity, cardiovascular disease, and neurodegenerative disorders [22][30] Group 1: Microbiome and Health - The gut microbiome consists of over 30 trillion microbes, comparable in number to human cells, and plays a crucial role in digestion and nutrient absorption [5][10] - Changes in the microbiome can occur rapidly in response to diet, antibiotics, and environmental factors, affecting overall health and resilience [8][13] - Dysbiosis can lead to increased intestinal permeability, systemic inflammation, and is associated with conditions like metabolic syndrome and autoimmune diseases [22][23][24] Group 2: Chronic Diseases Linked to Dysbiosis - Cardiovascular disease is linked to dysbiosis through microbial metabolites such as trimethylamine N-oxide (TMAO), which is associated with higher risks of heart attack and stroke [25][31] - Neurodegenerative diseases like Alzheimer's and Parkinson's show microbial shifts that may precede clinical symptoms, suggesting potential for early intervention [28][51] - Mental health issues, including major depressive disorder, have been correlated with reduced levels of beneficial gut bacteria [27][32] Group 3: Dietary Influence on the Microbiome - A diverse, plant-based diet rich in fiber, resistant starches, and polyphenols is essential for maintaining a healthy microbiome [35][39][54] - Fermented foods can enhance microbial diversity and reduce inflammation, supporting overall gut health [38][54] - Long-term dietary changes are necessary to achieve lasting improvements in microbiome composition, as short-term diets often revert to baseline [42][44] Group 4: Future of Microbiome Research and Therapies - Precision probiotics and live biotherapeutic products (LBPs) are being explored as potential treatments for metabolic and neurological disorders [46][49] - Emerging diagnostics, such as stool sequencing and capsule-based sampling, may allow for personalized microbiome-targeted therapies [51][52] - The integration of diet, lifestyle, and microbial therapeutics is anticipated to be the future approach for optimizing gut health and overall well-being [52][53]

Core Viewpoint - The article discusses the relationship between nasal microbiota, specifically Staphylococcus aureus, and depressive behavior, highlighting the role of sex hormone degradation in this process [4][5][11]. Group 1: Research Findings - A study published in Nature Microbiology indicates that nasal Staphylococcus aureus can promote depressive behavior in mice by degrading sex hormones [4][5]. - The enzyme 17β-hydroxysteroid dehydrogenase expressed by Staphylococcus aureus degrades testosterone and estradiol in mice, leading to decreased levels of dopamine and serotonin in the brain, which induces depressive-like behavior [5][11]. - Analysis of nasal microbiota shows a positive correlation between the abundance of Staphylococcus aureus and depression scores in both depressed patients and healthy controls [9]. Group 2: Implications - The findings suggest a significant link between nasal microbiota and brain function, particularly in the context of neuropsychiatric disorders, which has been under-researched [8]. - The study provides new insights into the nose-brain axis, indicating that nasal colonization by certain bacteria may influence mental health through hormonal pathways [11].

Core Insights - The research from the Charles Perkins Centre at the University of Sydney suggests that gut microbiome health may be influenced by genetics, not just diet, highlighting the role of a natural protein peptide called α-defensin in managing gut bacteria and protecting against unhealthy diets [1][2][3] Group 1: Research Findings - The study indicates that certain genes in mice lead to the production of α-defensin, which helps promote beneficial bacteria while eliminating harmful ones, resulting in healthier gut microbiomes and reduced risk of insulin resistance [1][2] - Mice that produced more α-defensin were found to be healthier compared to those that produced less, and synthetic α-defensin peptides were shown to protect mice from the negative effects of unhealthy diets [2] - The research emphasizes that while gut microbiomes influence various diseases, the body actively shapes its microbiome through genetic factors, suggesting potential for peptide-based treatments for chronic diseases like diabetes and obesity [2][3] Group 2: Implications for Personalized Medicine - The study highlights the importance of personalized medicine, indicating that individuals with different genetic backgrounds may respond differently to treatments involving defensin peptides [2][3] - The research team is expanding their studies to explore the application of α-defensin in human health, particularly its relationship with metabolic health and gut microbiomes [3] - The potential for precision medicine is underscored, as understanding individual responses to treatments could lead to more effective interventions for managing gut microbiomes and associated chronic diseases [3]

Core Viewpoint - The research highlights the importance of gut microbiota in enhancing the efficacy and safety of immune checkpoint blockade (ICB) therapy for cancer treatment, proposing a novel food-medicine homologous formula to improve outcomes and reduce adverse effects [2][6][10]. Group 1: Research Development - A new oral formulation, CV/APS-MS, was developed using microcapsules to co-load Chlorella vulgaris and Astragalus polysaccharides, which are recognized for their therapeutic and nutritional benefits [3][6]. - This formulation aims to prolong retention time in the gut, nourish beneficial gut microbiota, and alleviate inflammation [6][8]. Group 2: Experimental Findings - In mouse models of melanoma lung metastasis treated with ICB therapy, CV/APS-MS improved T cell-mediated anti-tumor immunity and mitigated ICB-induced colitis and pneumonia by restoring gut microbiota balance and reducing pro-inflammatory cytokines [8][10]. - The study suggests that combining food-grade bioreagents with modern medicine could be a powerful method to enhance cancer treatment efficacy and tolerance [10].

Core Viewpoint - The emergence of immunotherapy has significantly changed the landscape of cancer treatment, but resistance to immunotherapy remains a major obstacle for its broader clinical application. Recent studies indicate that gut microbiota can enhance the efficacy of immunotherapy by modulating anti-tumor immunity [2]. Group 1: Research Findings - A study published by Professor Xu Ruihua's team from Sun Yat-sen University on July 24, 2025, in the journal Cancer Cell, demonstrates that the gut bacterium Alistipes finegoldii can enhance the efficacy of immunotherapy against solid tumors [3][4]. - The research found that a higher abundance of Alistipes finegoldii is associated with improved responses to immunotherapy, particularly enhancing the efficacy of anti-PD-1 monoclonal antibodies in solid tumor models [8]. - Alistipes finegoldii activates the CXCL16-CXCR6 signaling axis to boost anti-tumor immune responses, with lipoproteins derived from Alistipes finegoldii triggering the TLR2-NF-κB-CXCL16 signaling pathway [7][8]. Group 2: Mechanism of Action - The mechanism involves lipoproteins from Alistipes finegoldii binding to Toll-like receptor 2 (TLR2), activating the NF-κB signaling pathway, which enhances the expression of CXCL16 in CCR7+ conventional dendritic cells [7]. - The released CXCL16 aids in recruiting CXCR6+ CD8+ T cells to the tumor microenvironment (TME), effectively inhibiting tumor growth [7][8]. Group 3: Implications for Treatment - Overall, the findings suggest that combining Alistipes finegoldii with immunotherapy could represent a new strategy for treating solid tumors [10].

Core Viewpoint - The study highlights the impact of gut microbiota dysbiosis induced by brain tumors on the efficacy of immunotherapy, suggesting that dietary supplementation with tryptophan can restore gut microbiota and significantly enhance the immune response through T cell circulation [2][11][14]. Group 1: Research Background - The influence of gut microbiota on various tumors, particularly gastrointestinal tumors, is recognized, but its effects on brain tumors remain largely unexplored [2][6]. - Glioblastoma (GBM) is known for its poor prognosis and limited survival rate improvements despite various treatments, attributed to unique characteristics of the tumor microenvironment [4][5]. Group 2: Research Findings - The research utilized a GBM mouse model and employed 16S rRNA sequencing to analyze changes in gut microbiota during tumor progression, finding that tryptophan supplementation could reverse these changes [9]. - Tryptophan supplementation not only restored gut microbiota balance but also significantly improved survival rates in mouse models and enhanced the effectiveness of immunotherapy [9][13]. Group 3: Key Microbial Insights - Among the gut bacteria responding positively to tryptophan, Duncaniella dubosii emerged as a key contributor to the immune modulation effects of tryptophan [10][13]. - The study emphasizes the potential of targeting gut microbiota modulation to improve cancer immunotherapy outcomes, particularly through mechanisms involving T cell regulation [14].