Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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.

Centenarian-Sourced Lactobacillus casei Combined with Dietary Fiber Complex Ameliorates Brain and Gut Function in Aged Mice

Dietary intervention could modulate age-related neurological disorders via the gut–brain axis. The potential roles of a probiotic and the dietary fiber complex (DFC) on brain and gut function in aged mice were investigated in this study. Lactobacillus casei LTL1361 and DFC were orally administrated for 12 weeks, and the learning and memory ability, as well as the oxidative parameters, inflammatory markers, gut barrier function and microbial metabolite short-chain fatty acids (SCFAs), were investigated. LTL1361 and DFC supplementation ameliorated cognitive ability, attenuated oxidative stress in brain and inflammation in serum and colon, ameliorated gut barrier function, and increased the SCFA concentrations and gene expression of SCFA receptors. The protective effect was more significantly enhanced in aged mice treated with the combination of LTL1361 and DFC than treated with LTL1361 or DFC alone. These results could be associated with the protected morphology of pyramidal nerve cells in hippocampus of mice brain and the downregulation of apoptosis marker caspase-3 in brain and upregulation of tight junction proteins in small intestine and colon. The results indicated that Lactobacillus casei LTL1361 and DFC alleviated age-related cognitive impairment, as well as protected brain and gut function. Lactobacillus casei LTL1361 and DFC might be used as novel and promising antiaging agents in human.

Osteoarthritis improvement effect of Chrysanthemum zawadskii var. latilobum extract in relation to genotype

Objectives: To determine whether SNPs of osteoarthritis (OA)-related genes predict the effect of Chrysanthemum zawadskii var. latilobum (CZ) extract in OA patients with OA. Subjects/methods: To analyze correlations between CZ extract effects in humans and their genotypes, 121 Korean patients with OA were recruited. Patients ingested 600 mg/day of the CZ extract GCWB106 (one tablet daily), including 250-mg CZ, or placebo (one tablet daily) for 12 weeks. Twenty SNPs were genotyped in 11 genes associated with OA pathogenesis, including tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinases (MMPs), and 9 genes involved in OA-related dietary intervention. The Visual Analogue Scale (VAS) and Korean Western Ontario and McMaster Universities (K-WOMAC) were measured as indicators of GCWB106 effect. Statistical comparisons were performed using Kruskal-Wallis tests to identify associations between these scales and genotyped loci in patients with OA. Results: Three SNPs ( PPARG rs3856806, MMP13 rs2252070, and ZIP2 rs2234632) were significantly associated with the degree of change in VAS pain score. Homozygous CC genotype carriers of rs3856806, G allele carriers (GA or GG) of rs2252070, and T allele carriers (GT or TT) of rs2234632 showed lower VAS score (i.e., less severe symptoms) in the GCWB106 group (n=53) than the placebo group (n=57) (p=0.026, p=0.009, and p=0.025, respectively). Gene–gene interaction effects on GCWB106-mediated pain relief were then examined, and it was found that the addition of each genotype resulted in a greater decrease in VAS pain score in the GCWB106 group (p=0.0024) but not the placebo group (p=0.7734). Conclusions: These novel predictive markers for the pain-relieving effects of GCWB106 may be used in the personalized treatment of patients with OA.

A Pilot Study of Gene Expression Analysis in Peripheral Blood Mononuclear Cells in Response to a Hypocaloric Mediterranean Diet

Background. Few studies have examined gene expression in peripheral blood mononuclear cells (PBMCs) after a dietary intervention. Objective. Our study is aimed at evaluating in a pilot study the peripheral blood gene expression in obese patients after weight loss secondary to a hypocaloric Mediterranean diet. Design. A sample of 11 obese subjects without metabolic syndrome was enrolled. Biochemical, anthropometric parameters and microarray analysis were performed at baseline and after 6 months of dietary intervention. Results. The mean age was 43.1 ± 6.3 years, and the mean body mass index (BMI) was 38.6 ± 8.1 kg/m2. All the next improvements were statistically significant: body weight − 7.4 ± 1.9 kg, BMI - 2.5 ± 0.2 kg, fat mass − 5.7 ± 1.2 kg, waist circumference − 5.8 ± 1.2 cm, triglycerides − 17.4 ± 6.5 mg/dl, C-reactive protein − 3.1 ± 1.5 mg/dL, insulin − 2.1 ± 1.0 mUI/L, and HOMA-IR − 0.7 ± 0.2 units. We identified 634 differentially expressed genes: 262 genes with relative higher expression levels and 372 with lower expression levels. Cluster analysis showed 35 genes in nutritional disease and 17 genes in endocrine system. The most relevant gene was thyroid peroxidase (TPO), and this gene was overexpressed, and the next genes carbonic anhydrase VI (CA6), caveolin protein 1 (CAV1) and solute carrier family type 12 (SLLC12A3), soluble carrier family type 12 (SLLC12A3), beta 3 receptor (ADRB3), and glutamate receptor ionotropic N methyl D aspartate 2 A (GRIN2A) were all underexpressed. Conclusion. In PBMC from obese patients after a diet with a Mediterranean pattern, the expression of 634 genes, of the endocrine system and of nutritional disease, is modified.

Physiological Effects of Bioactive Compounds Derived from Whole Grains on Cardiovascular and Metabolic Diseases

Cardiovascular diseases are a global health burden with an increasing prevalence. In addition, various metabolic diseases, such as obesity, diabetes, and hypertension are associated with a higher risk of cardiovascular diseases. Dietary strategies based on healthy foods have been suggested for the prevention or improvement of cardiovascular and metabolic diseases. Grains are the most widely consumed food worldwide, and the preventive effects of whole grains (e.g., oats, barley, and buckwheat) on metabolic diseases have been reported. The germ and bran of grains are rich in compounds, including phytochemicals, vitamins, minerals, and dietary fiber, and these compounds are effective in preventing and improving cardiovascular and metabolic diseases. Thus, this review describes the characteristics and functions of bioactive ingredients in whole grains, focusing on mechanisms by which polyphenols, antioxidants, and dietary fiber contribute to cardiovascular and metabolic diseases, based on preclinical and clinical studies. There is clear evidence for the broad preventive and therapeutic effects of whole grains, supporting the value of early dietary intervention.

Effect of a dietary intervention including minimal and unprocessed foods, high in natural saturated fats, on the lipid profile of children, pooled evidence from randomized controlled trials and a cohort study

Aim To study the possible effects of a dietary intervention with minimal and unprocessed foods, high in natural saturated fats on the lipid profile and body mass index of children. Method This study combines three intervention studies; one non-randomized retrospective cohort study and two randomized controlled trials, to a pooled analysis. The intervention group received a dietary intervention of minimal and unprocessed foods for three to six months, consisting of five times per week green vegetables, three times per week beef, daily 200–300 mL whole cow’s milk (3.4% fat) and whole dairy butter (80% fat) on each slice of bread. The control group continued their usual dietary habits. Raw data of the three intervention studies where combined into one single dataset for data analysis, using mixed effects analysis of covariance to test the effects of the dietary advice on the main study outcomes, which are measurements of the lipid profile. Results In total, 267 children aged 1 to 16 years were followed. 135 children were included in the intervention group and 139 children in the control group. Characteristics (age, gender and follow-up period) were equally distributed between the groups at baseline. In the intervention group HDL-cholesterol increased significantly from 1.22 mmol/L, 95% confidence interval (CI) 1.14–1.32 to 1.42 mmol/L 95% CI 1.30–1.65 (p = 0.007). The increase over time in HDL cholesterol in the intervention group was significantly different compared to the increase in the control group (from 1.26 mmol/L, 95% CI 1.19–1.35, to 1.30 mmol/L, 95% CI 1.26–1.37) (p = 0.04). Due to the increased HDL concentration in the intervention group, the total cholesterol/HDL cholesterol ratio decreased significantly from 3.70 mmol/L, 95% CI 3.38–3.87, to 3.25 mmol/L, 95% CI 2.96–3.31 (p = 0.05). Conclusion Consumption of minimal and unprocessed foods (high in natural saturated fats) has favourable effects on HDL cholesterol in children. Therefore, this dietary advice can safely be recommended to children.

Impact of Dietary Sodium Butyrate and Salinomycin on Performance and Intestinal Microbiota in a Broiler Gut Leakage Model

Unfavorable alterations of the commensal gut microbiota and dysbacteriosis is a major health problem in the poultry industry. Understanding how dietary intervention alters the microbial ecology of broiler chickens is important for prevention strategies. A trial was conducted with 672 Ross 308 day-old male broilers fed a basic diet (no additives, control) or the basic diet supplemented with 500 mg/kg encapsulated butyrate or 68 mg/kg salinomycin. Enteric challenge was induced by inclusion of 50 g/kg rye in a grower diet and oral gavage of a 10 times overdose of a vaccine against coccidiosis. Compared to control and butyrate-supplemented birds, salinomycin supplementation alleviated growth depression. Compared to butyrate and non-supplemented control, salinomycin increased potentially beneficial Ruminococcaceae and reduced potentially pathogenic Enterobacteriaceae and counts of Lactobacillus salivarius and Clostridium perfringens. Further, salinomycin supplementation was accompanied by a pH decrease and succinic acid increase in ceca, while coated butyrate (0.5 g/kg) showed no or limited effects. Salinomycin alleviated growth depression and maintained intestinal homeostasis in the challenged broilers, while butyrate in the tested concentration showed limited effects. Thus, further investigations are required to identify optimal dietary inclusion rates for butyrate used as alternative to ionophore coccidiostats in broiler production.

The role of CD36-Fabp4-PPARγ in skeletal muscle involves insulin resistance in intrauterine growth retardation mice with catch-up growth

Background Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society. Methods The pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes. Results After dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05). Conclusions LBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways.

Protective effects of bioactive peptides in foxtail millet protein hydrolysates against experimental colitis in mice

It is of great significance to develop a dietary intervention strategy to prevent inflammatory bowel disease (IBD). A millet-rich diet can ameliorate IBD, but the active ingredients and mechanisms remain...