Probiotics and Bone Health - Role of Gender and Intestinal Health

益生菌和骨骼健康 - 性别和肠道健康的作用

• 批准号: 7991060
• 负责人: ROBERT A BRITTON
• 金额: $ 22.8万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991060
• 关键词: Address; Adult; Age; Aging; American; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Artificial Implants; Asthma; Attenuated; Back; Bacteria; Bacterial Toxins; Biological Factors; Biological Response Modifier Therapy; Bone Density; Bone Resorption; Bone remodeling; Calcium; Characteristics; Child; Communication; Cystic Fibrosis; Data; Dependency; Diarrhea; Digestion; Disease; Estrogens; Female; Fracture; Gastrointestinal Hormones; Gastrointestinal tract structure; Gender; Gender Role; Gene Expression; Gonadal Steroid Hormones; Healed; Health; Health Benefit; Histology; Hormones; Hypersensitivity; Immune system; Individual; Inflammation; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Ingestion; Insulin-Dependent Diabetes Mellitus; Intestines; Investigation; Knowledge; Lactobacillus reuteri; Lead; Measurement; Measures; Mediating; Mental Depression; Metabolic; Metabolism; Minerals; Modeling; Mucositis; Mus; Orchiectomy; Osteitis; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Pharmaceutical Preparations; Postmenopause; Probiotics; Progesterone; Property; RNA; Regulation; Risk; Role; Serotonin; Serum; Serum Calcium Level; Signal Transduction; Steroids; Structure; TNF gene; Testing; Therapeutic; Time; United States; Up-Regulation; Woman; absorption; base; bone; bone health; bone loss; bone mass; calcium absorption; cytokine; density; gastrointestinal; healing; ileum; improved; insulin secretion; male; men; microbial community; microorganism; novel; osteoporosis with pathological fracture; prevent; public health relevance; response

DESCRIPTION (provided by applicant): Over 40 million Americans (14 million of which are men) of all ages are afflicted with low bone density and its associated increased risk of fractures. While aging is a major cause of osteoporosis, diseases (such as type I diabetes, cystic fibrosis, asthma, inflammatory bowel disease, and arthritis), inactivity, poor dietary choices, and certain medications can cause bone loss at any age. Recent studies demonstrate that bone communications with the intestine. Potential mechanisms include signaling to bone through gastrointestinal (GI) hormones and calcium absorption. Recently, we found another interaction: GI inflammation leads to increased bone inflammation, which is associated with suppressed bone formation and bone loss in mice. This suggests that therapies which improve overall intestinal health have the potential to benefit bone health. Identifying natural products that could help individuals attain their maximum bone mass and suppress bone loss would be of great preventative and therapeutic value. Probiotics, microorganisms that provide a health benefit to the host when ingested, are used to treat a wide variety of ailments ranging from diarrhea to allergies. These microorganisms may boost the immune system, reduce colonization of harmful bacteria in the intestine, destroy certain bacterial toxins, decrease intestinal inflammation and help with digestion and mineral absorption. To address the effects probiotics on bone, we administered an anti- inflammatory probiotic strain, Lactobacillus reuteri ATCC PTA 6475, to adult mice and measured their bone densities. Fascinatingly, we found that L. reuteri treatment decreased TNF levels in the ileum and increased bone volume by greater than 45% in healthy male but not female mice. Based on our data we hypothesize that ingestion of L. reuteri increases bone density in a gender dependent manner through suppression of intestinal inflammation and upregulation of bone formation. We further hypothesize that sex hormones and changes in other intestinal signals (microbiota composition, hormones, and calcium status) contribute to the bone response. We propose to test our hypotheses by 1) Identifying the influence of gender on bone responses to L. reuteri treatment and 2) Identifying characteristics of probiotic L. reuteri and its effects on the gastrointestinal tract which are critical for enhancing bone mass. Few studies have examined probiotic effects on bone, and none have included an extensive analysis of bone, serum and GI parameters. Our studies will fill this gap in knowledge by identifying basic mechanisms relating the GI tract to bone health and will test the influences of gender in this linkage. Given the increasing use of probiotics in the United States and worldwide, our findings warrant further investigation into the effects of probiotic use on bone health in males and females. PUBLIC HEALTH RELEVANCE: Finding effective novel treatments for bone loss is a priority, since it is estimated that by 2020 more than 61 million men and women will have osteoporosis and its associated increase in fracture risk and potential negative effects on metabolism and insulin secretion. We have identified a novel way of increasing bone mass by use of a probiotic bacterium that attenuates intestinal inflammation. If proven effective, it could lead to a significant improvement in the health and well being of people with decreased bone density.

描述（由申请人提供）：所有年龄段的超过4000万美国人（其中1400万人）患有低骨密度及其相关的骨折风险增加。尽管衰老是造成骨质疏松症的主要原因，但疾病（例如I型糖尿病，囊性纤维化，哮喘，炎症性肠病和关节炎），不活动，饮食选择不佳以及某些药物可能会导致任何年龄段的骨质流失。最近的研究表明，骨与肠道通信。潜在的机制包括通过胃肠道（GI）激素和钙吸收的信号传导。最近，我们发现了另一种相互作用：胃肠道炎症会导致骨骼炎症增加，这与小鼠的骨骼形成和骨质流失有关。这表明改善整体肠道健康的疗法有可能使骨骼健康受益。确定可以帮助个人达到最大骨骼并抑制骨质流失的天然产品将具有很大的预防和治疗价值。益生菌，在摄入时为宿主提供健康益处的微生物，用于治疗从腹泻到过敏的各种疾病。这些微生物可能会增强免疫系统，减少肠道中有害细菌的定殖，破坏某些细菌毒素，减少肠道炎症并帮助消化和矿物质吸收。为了解决益生菌对骨骼的影响，我们对成年小鼠施用了抗炎性益生菌菌株Reuteri ATCC PTA 6475，并测量其骨密度。令人着迷的是，我们发现，REUTERI治疗在健康男性但没有增加的雌性小鼠中降低了回肠的TNF水平，骨体积增加了45％以上。基于我们的数据，我们假设摄入R. Reuteri的摄入通过抑制肠道炎症和骨形成的上调，以性别依赖性的方式增加了骨密度。我们进一步假设性激素和其他肠道信号（微生物群，激素和钙状态）的变化有助于骨反应。我们建议通过1）确定性别对Reuteri治疗的骨骼反应的影响； 2）鉴定益生菌L. reuteri的特征及其对胃肠道的影响，这对于增强骨骼至关重要。很少有研究检查对骨骼的益生菌作用，而没有研究对骨，血清和胃肠道参数进行广泛的分析。我们的研究将通过确定将胃肠道与骨骼健康相关的基本机制来填补这一差距，并将测试性别在这种联系中的影响。鉴于美国和全球益生菌的使用越来越多，我们的发现需要进一步研究益生菌对男性和女性骨骼健康的影响。 公共卫生相关性：找到有效的骨质损失的新型治疗方法是一个优先事项，因为据估计，到2020年，有超过6100万的男性和女性将患有骨质疏松症，并且与骨折风险和对代谢和胰岛素分泌的潜在负面影响相关的增加。我们已经通过使用减轻肠道炎症的益生菌细菌来确定一种增加骨骼质量的新方法。如果被证明有效，它可能会导致骨密度降低的人的健康和福祉显着改善。