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1.
Direct Modulation of the Gut Microbiota as a Therapeutic Approach for Alzheimer's Disease.
Wang, Y, Dykes, GA
CNS & neurological disorders drug targets. 2022;(1):14-25
Abstract
Alzheimer's disease is a neurodegenerative disease characterized by a progressive decline in memory and cognitive functions. It is a multifactorial disease involving a wide range of pathological factors that are not fully understood. As supported by a growing amount of evidence in recent years, gut microbiota plays an important role in the pathogenesis of Alzheimer's disease through the brain-gut-microbiota axis. This suggests that direct modulation of the gut microbiota can be a potential therapeutic target for Alzheimer's disease. This review summarizes recent research findings on the modulation of the gut microbiota by probiotic therapies and faecal microbiota transplantation for controlling the pathologies of Alzheimer's disease. Current limitations and future research directions of this field are also discussed.
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2.
Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Sanchez, P, Letarouilly, JG, Nguyen, Y, Sigaux, J, Barnetche, T, Czernichow, S, Flipo, RM, Sellam, J, Daïen, C
Nutrients. 2022;(2)
Abstract
BACKGROUND We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). METHODS A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. RESULTS The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) -3.04 (95% CI -4.47, -1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD -0.54; 95% CI -1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. CONCLUSIONS Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies' heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.
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3.
Mucositis reduction with probiotics in children with cancer: a randomised-controlled feasibility study.
Hassan, H, Kinsey, S, Phillips, B
Archives of disease in childhood. 2022;(3):259-264
Abstract
BACKGROUND A recent systematic review and meta-analysis identified a paucity of randomised-controlled trials (RCTs) investigating the use of probiotics to reduce or prevent mucositis and infection in children with cancer. OBJECTIVE This study evaluated the feasibility of undertaking an RCT and investigated the efficacy of probiotics for reducing or preventing mucositis and infection in children with cancers. SETTING The Paediatric Oncology and Haematology department at Leeds Teaching Hospital, UK. PATIENTS Children aged 1 year or older, receiving chemotherapies likely to cause mucositis. INTERVENTIONS Participants were randomised to receive the probiotic or placebo on day 1-14 of a chemotherapy cycle. Participants were also required to complete a patient diary for 21 days. MAIN OUTCOME MEASURES To assess whether it is feasible to recruit children diagnosed with cancer who are at risk of developing mucositis to an adequately powered RCT. RESULTS Between May and November 2019, 34 out of 39 eligible participants were approached. Ten patients were recruited (4 probiotic and 6 placebo) of which 2 participants withdrew. Seven participants partially completed the diary but only two participants completed 80% or more. Eligible participants appeared to prefer giving informal verbal feedback when in direct contact with research and healthcare professionals. CONCLUSION This study demonstrated that recruitment needs to be improved prior to undertaking an adequately powered RCT. TRIAL REGISTRATION NUMBER NCT03785938.
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4.
Opioids and Sepsis: Elucidating the Role of the Microbiome and microRNA-146.
Abu, Y, Vitari, N, Yan, Y, Roy, S
International journal of molecular sciences. 2022;(3)
Abstract
Sepsis has recently been defined as life-threatening organ dysfunction caused by the dysregulated host response to an ongoing or suspected infection. To date, sepsis continues to be a leading cause of morbidity and mortality amongst hospitalized patients. Many risk factors contribute to development of sepsis, including pain-relieving drugs like opioids, which are frequently prescribed post-operatively. In light of the opioid crisis, understanding the interactions between opioid use and the development of sepsis has become extremely relevant, as opioid use is associated with increased risk of infection. Given that the intestinal tract is a major site of origin of sepsis-causing microbes, there has been an increasing focus on how alterations in the gut microbiome may predispose towards sepsis and mediate immune dysregulation. MicroRNAs, in particular, have emerged as key modulators of the inflammatory response during sepsis by tempering the immune response, thereby mediating the interaction between host and microbiome. In this review, we elucidate contributing roles of microRNA 146 in modulating sepsis pathogenesis and end with a discussion of therapeutic targeting of the gut microbiome in controlling immune dysregulation in sepsis.
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5.
The potential of probiotics in the amelioration of hyperuricemia.
Zhao, H, Lu, Z, Lu, Y
Food & function. 2022;(5):2394-2414
Abstract
Hyperuricemia is a common disease caused by metabolic disorders or the excessive intake of high-purine foods. Persistent hyperuricemia in extreme cases induces gout, and asymptomatic hyperuricemia is probably linked to other metabolic diseases, such as hypertension. The typical damage caused by asymptomatic hyperuricemia includes inflammation, oxidative stress and gut dysbiosis. Probiotics have broad potential applications as food additives, not as drug therapies, in the amelioration of hyperuricemia. In this review, we describe novel methods for potential hyperuricemia amelioration with probiotics. The pathways through which probiotics may ameliorate hyperuricemia are discussed, including the decrease in uric acid production through purine assimilation and XOD (xanthine oxidase) inhibition as well as enhanced excretion of uric acid production by promoting ABCG2 (ATP binding cassette subfamily G member 2) activity, respectively. Three possible probiotic-related therapeutic pathways for alleviating the syndrome of hyperuricemia are also summarized. The first mechanism is to alleviate the oxidation and inflammation induced by hyperuricemia through the inhibition of NLRP3 inflammasome, the second is to restore damaged intestinal epithelium barriers and prevent gut microbiota dysbiosis, and the third is to enhance the innate immune system by increasing the secretion of immunoglobulin A (sIgA) to resist the stimulus by hyperuricemia. We propose that future research should focus on superior strain resource isolation and insight into the cause-effect mechanisms of probiotics for hyperuricemia amelioration. The safety and effects of the application of probiotics in clinical use also need verification.
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6.
Health improvements of type 2 diabetic patients through diet and diet plus fecal microbiota transplantation.
Su, L, Hong, Z, Zhou, T, Jian, Y, Xu, M, Zhang, X, Zhu, X, Wang, J
Scientific reports. 2022;(1):1152
Abstract
Type 2 diabetes (T2D) is a major public health problem, and gut microbiota dysbiosis has been implicated in the emergence of T2D in humans. Dietary interventions can indirectly influence the health status of patients with type 2 diabetes through their modulatory effects on the intestinal microbiota. In recent years, fecal microbiota transplantation is becoming familiar as a new medical treatment that can rapidly improve intestinal health. We conducted a 90-day controlled open-label trial to evaluate the health improvement ability of a specially designed diet, and the diet combined with fecal microbiota transplantation (FMT). According to our study, both diet and diet plus FMT treatments showed great potential in controlling blood glucose and blood pressure levels. Sequencing the V4 region of 16S rRNA gene on the Illumina MiniSeq platform revealed a shift of intestinal microbial community in T2D patients, and the changes were also observed in response to the treatments. FMT changed the gut microbiota more quickly than diet. Beneficial bacterium, such as Bifidobacterium, increased along the study and was negatively correlated with blood glucose, blood pressure, blood lipid and BMI. Sulfate-reducing bacteria (SRB), Bilophila and Desulfovibrio, decreased significantly after treatment, showed a positive correlation with blood glucose indices. Thus, the specially designed diet is beneficial to improve blood glucose control in diabetic patients, it also showed the potential to reverse dyslipidemia and dysarteriotony.
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7.
Shaping the gut microbiota by bioactive phytochemicals: An emerging approach for the prevention and treatment of human diseases.
Sudheer, S, Gangwar, P, Usmani, Z, Sharma, M, Sharma, VK, Sana, SS, Almeida, F, Dubey, NK, Singh, DP, Dilbaghi, N, et al
Biochimie. 2022;:38-63
Abstract
The human digestive tract is the cottage to trillions of live microorganisms, which regulate health and illness. A healthy Gut Microbiota (GM) is necessary for preventing microbial growth, body growth, obesity, cancer, diabetes, and enhancing immunity. The equilibrium in GM's composition and the presence/absence of critical species enable specific responses to be essential for the host's better health condition. Research evidences revealed that the dietary plants and their bioactive phytochemicals (BPs) play an extensive and critical role in shaping the GM to get beneficial health effects. BPs are also known to improve gastrointestinal health and reduce the risk of several diseases by modulating GM-mediated cellular and molecular processes. Regular intake of BPs-rich vegetables, fruits, and herbal preparations promotes probiotic bacteria, including Bifidobacteria and Lactobacillus species, while inhibiting unwanted gut residents' development Escherichia coli, and Salmonella typhimurium etc. Upon consumption, BPs contact the GM that gets transformed before being absorbed from the gastrointestinal tract. Biotransformation of BPs by GM is linked with the enhancement of bioactivity/toxicity diminishment of the BPs compared to parental phytochemicals. Therefore, the current review focuses on the role of BPs in shaping GM for the prevention and treatment of human diseases.
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8.
Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial.
Fernández-Ferreiro, A, Formigo-Couceiro, FJ, Veiga-Gutierrez, R, Maldonado-Lobón, JA, Hermida-Cao, AM, Rodriguez, C, Bañuelos, O, Olivares, M, Blanco-Rojo, R
Nutrients. 2022;(1)
Abstract
Elderly people are particularly vulnerable to COVID-19, with a high risk of developing severe disease and a reduced immune response to the COVID-19 vaccine. A randomized, placebo-controlled, double-blind trial to assess the effect of the consumption of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on the immune response generated by the COVID-19 vaccine in an elderly population was performed. Two hundred nursing home residents >60 yrs that had not COVID-19 were randomized to receive L. coryniformis K8 or a placebo daily for 3 months. All volunteers received a complete vaccination schedule of a mRNA vaccine, starting the intervention ten days after the first dose. Specific IgG and IgA antibody levels were analyzed 56 days after the end of the immunization process. No differences between the groups were observed in the antibody levels. During the intervention, 19 subjects had COVID-19 (11 receiving K8 vs. 8 receiving placebo, p = 0.457). Subgroup analysis in these patients showed that levels of IgG were significantly higher in those receiving K8 compared to placebo (p = 0.038). Among subjects >85 yrs that did not get COVID-19, administration of K8 tended to increase the IgA levels (p = 0.082). The administration of K8 may enhance the specific immune response against COVID-19 and may improve the COVID-19 vaccine-specific responses in elderly populations.
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9.
A Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Efficacy and Safety of Lactiplantibacillus plantarum CJLP243 in Patients with Functional Diarrhea and High Fecal Calprotectin Levels.
Jung, M, Jung, S, Kim, N, Ahn, H, Yun, H, Kim, KN
Nutrients. 2022;(2)
Abstract
Micro-inflammation in the gut, assessed by fecal calprotectin (FC), is considered a component of the pathogenesis of functional diarrhea (FD). Since probiotics may suppress micro-inflammation in the intestine by competing with harmful bacteria, we hypothesized that they would reduce the ratio of loose stool symptoms and gut inflammation in patients with FD. We conducted a double-blind, placebo-controlled trial to assess the clinical and laboratory effects of Lactobacillus plantarum CJLP243 in FD patients with elevated FC levels for two months. Twenty-four patients diagnosed with FD with elevated FC levels were randomly assigned to either a probiotic group or a placebo group. After 2 months, 10 patients in the probiotic group and 12 patients in the placebo group completed the study, and FD symptoms, FC values, and intestinal flora were re-evaluated in these subjects. The percentage of subjects who had adequate FD relief (decrease in loose stool frequency) in the probiotic group was significantly increased after two months compared with the baseline. In addition, the probiotic group showed a statistically significant decrease in log-transformed FC values compared with the pre-treatment group, whereas the placebo group showed no difference before and after the intervention. Furthermore, the levels of Leuconostoc genus organisms in the gut microbiota composition in the probiotic group increased significantly after the end of the study compared with the baseline values. In this preliminary exploratory research, we found that two months of Lactiplantibacillus plantarum CJLP243 treatment resulted in FD symptom improvement, reduced FC values, and increased Leuconostoc levels, suggesting that the intake of Lactiplantibacillus plantarum was helpful in those patients. These findings need to be validated via further clinical studies.
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10.
Meta-analysis of randomized controlled trials of the effects of probiotics on type 2 diabetes in adults.
Zhang, C, Jiang, J, Wang, C, Li, S, Yu, L, Tian, F, Zhao, J, Zhang, H, Chen, W, Zhai, Q
Clinical nutrition (Edinburgh, Scotland). 2022;(2):365-373
Abstract
BACKGROUND & AIMS Despite advancements in preventive medicine and pharmacotherapy, diabetes remains an overwhelming health problem. Evidence from randomized controlled trials (RCTs) suggests that probiotics may offer beneficial effects on glycemic control. Our objective was to perform a systematic review and meta-analysis of RCTs to quantify the effect of probiotic administration on glycemic homeostasis in type 2 diabetes. METHODS Medline, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for relevant trials published until October 12, 2021. RCTs that lasted ≥3 weeks and assessed the effects of probiotics on the markers of glycemic homeostasis in type 2 diabetes were included. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q statistic and quantified using the I2 statistic. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. RESULTS A total of 33 eligible trial comparisons (n = 1927) were included in this meta-analysis. Our results revealed that compared with placebo, a median probiotic dose of ∼109 cfu/day significantly reduced the glycated hemoglobin (HbA1c) levels (MD: -0.19% [95% CI: -0.32, -0.07]; P = 0.003), fasting blood glucose levels (MD: -1.00 mmol/L [95% CI: -1.45, -0.56]; P < 0.0001), fasting insulin levels (MD: -5.73 pmol/L [95% CI: -12.17, 0.72]; P = 0.08), and HOMA-insulin resistance (IR) (MD: -1.00 [95% CI: -1.32, -0.68]; P < 0.00001). The certainty of evidence was graded low for HbA1c and fasting glucose, moderate for fasting insulin, and high for HOMA-IR. Probiotic supplements do not induce clinically significant reductions in HbA1c levels, but lead to marginally clinically significant reductions in fasting glucose and fasting insulin levels in patients with type 2 diabetes. Compared with single-strain and low-dose probiotics, multi-strain and high-dose probiotics have a greater beneficial effect on glycemic homeostasis. In addition, probiotic treatment may be more effective in patients with a high baseline body mass index and age.