-
1.
Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial.
Lecomte, M, Tomassi, D, Rizzoli, R, Tenon, M, Berton, T, Harney, S, Fança-Berthon, P
Nutrients. 2023;15(12)
-
-
-
Free full text
Plain language summary
Osteoporosis is a bone condition characterized by weakened and brittle bones, leading to an increased risk of fractures. Oestrogens play a vital role in maintaining bone health, whereby oestrogen deficiency elevates the risk of osteoporosis and fractures, particularly in menopausal women due to the decline in oestrogen levels. Phytoestrogens, plant-derived compounds capable of interacting with human oestrogen receptors, have presented an intriguing non-pharmaceutical avenue for preventing bone loss. Other phytoestrogens have received some attention in the field, however, limited human research exists on prenylflavonoids, a phytoestrogens found in hops (Humulus lupulus). This randomized, double-blinded, placebo-controlled trial aimed to investigate the effects of a year-long supplementation of standardised hop extract (8-PN) Lifenol® on bone mineral density in postmenopausal women. Additionally, the study explored potential mechanisms, particularly focusing on changes in gut bacteria. Notably, gut bacteria play a role in bone metabolism and the pathogenesis of osteoporosis. They are also, along with the liver, responsible for converting hops phenols into active phytoestrogenic compounds. The trial was completed by 95 postmenopausal, women with Osteopenia aged 50 to 85. They all received calcium and vitamin D3 tablets in addition either a hop extract (100mcg) or a placebo for 48 weeks. Changes were monitored using DXA scans for bone mineral density (BMD) and bone metabolism, blood samples for markers for bone health, a quality of life questionnaire, gut microbiome testing, and tests for short-chain fatty acid (SCFA) levels. In conclusion, the intake of hop extract confirmed a previously observed trend of a slight increase in total bone mineral density (BMD), in addition to the benefits linked to calcium and vitamin D supplementation. Although there were no significant changes in the composition of gut bacteria and SCFA levels, the hop extract candidates had a higher abundance of specific genera associated with total body BMD, suggesting a potential positive impact. Larger studies are required to validate these findings.
Abstract
Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant's quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.
-
2.
Effect of an enzyme-containing mouthwash on the dental biofilm and salivary microbiome in patients with fixed orthodontic appliances: a randomized placebo-controlled pilot trial.
Hoffstedt, T, Skov Hansen, LB, Twetman, S, Sonesson, M
European journal of orthodontics. 2023;45(1):96-102
-
-
-
Free full text
-
Plain language summary
Fixed orthodontic appliances are associated with dysbiosis in the oral cavity which may result in demineralisations of the enamel. Antiseptic mouthwashes have been shown to control the formation of cariogenic biofilm but may have negative effects on the salivary microbiome. The aim of this 8-day double-blind, randomised, placebo-controlled trial, including 35 adolescents with fixed orthodontics, was to evaluate the effect of an enzyme-based mouthwash (EBM), used twice daily, on dental biofilm (plaque) formation and salivary microbiome. At 8 days, a statistically and clinically significant decrease in the orthodontic plaque index was seen in the EBM group, whilst no change was seen in the placebo group. There were no statistically significant changes in microbiome between groups but a trend to increased richness in the placebo group. The authors concluded that the use of an enzyme-based mouthwash alongside regular toothbrushing reduced dental biofilm in adolescents with orthodontics without affecting the salivary microbiome.
Abstract
BACKGROUND Mouthwashes containing oral antiseptics or enzymes are suggested suitable for controlling biofilm accumulation in patients with fixed appliances and thereby limiting unwanted side effects during the orthodontic treatment. OBJECTIVES To evaluate the effect of an enzyme-based mouthwash on the amount of dental biofilm and the composition of the salivary microbiome in patients undergoing treatment with fixed orthodontic appliances. TRIAL DESIGN Randomized double-blind placebo-controlled trial. MATERIAL AND METHODS In total, 35 young adolescents (14-18 years) under treatment with fixed appliances were consecutively enrolled and randomly allocated to an experimental or a placebo group by opening a computer-generated numbered envelope. The subjects were instructed to rinse twice daily during an intervention period of 8 days with experimental mouthwash or placebo without active enzymes. Unstimulated whole saliva samples were collected at baseline and after 8 days. The participants and examiner were blinded for the allocation. The primary outcome was the Orthodontic Plaque Index (OPI) and the secondary was the composition of the salivary microbiome. RESULTS In total, 28 adolescents (21 females and 7 males) completed the trial and there were no differences in age, clinical, or microbial findings between the test (n = 14) and the placebo group (n = 14) at baseline. We found a decreased OPI in the test group after 8 days and the difference was statistically significant compared with the placebo group (P < 0.05). There were no significant treatment effects on the richness and global composition of the salivary microbiome. HARMS In total, one participant in the test group claimed nausea and abandoned the project. In total, two participants did not like the taste of the mouthwash but used it as instructed. No other adverse events or side effects were reported. LIMITATIONS Short-term pilot trials may by nature be sensitive for selection and performance biases and are not designed to unveil persisting effects. CONCLUSION Daily use of enzyme-containing mouthwash reduced the amount of dental biofilm in adolescents under treatment with the fixed orthodontic appliances, without affecting the composition of the salivary microbiota. ETHICAL APPROVAL Approved by the Regional Ethical Board, Lund, Sweden (Dnr 2020-05221). CLINICAL TRIAL REGISTRATION NCT05033015.
-
3.
Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial.
Schaub, AC, Schneider, E, Vazquez-Castellanos, JF, Schweinfurth, N, Kettelhack, C, Doll, JPK, Yamanbaeva, G, Mählmann, L, Brand, S, Beglinger, C, et al
Translational psychiatry. 2022;12(1):227
-
-
-
Free full text
Plain language summary
Major depressive disorder (MDD) is one of the most prevalent and burdensome psychiatric disorders. Compelling preclinical data indicate that the gut microbiota affects brain functions and depressive behaviour, providing a promising novel target for the treatment of depression. The aims of this study were to (i) examine the effect of a short-term, high-dose probiotic add-on therapy on depressive symptoms in MDD patients, and (ii) explore the effects of a probiotic supplementation on gut microbiota composition as well as brain structure and function. This study was a double-blind randomised controlled trial of a probiotic add-on therapy for four weeks in depressed patients. Patients (n=60) were randomly allocated to the two study groups and tested at three different time points. Results showed that an add-on probiotic treatment improves depressive symptoms and maintains healthy enterotypes, species richness and increases specific health related bacterial taxa. Furthermore, on a neural level, probiotics altered negative biases and emotional valence additionally to treatment-as-usual for depression. Authors conclude that their findings highlight the role of the microbiota-gut-brain axis in MDD and emphasises the potential of microbiota-related treatment approaches as therapies to improve the effectiveness of current treatments in depression.
Abstract
A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.
-
4.
Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis.
Di Palo, DM, Garruti, G, Di Ciaula, A, Molina-Molina, E, Shanmugam, H, De Angelis, M, Portincasa, P
Nutrients. 2020;12(2)
-
-
-
Free full text
Plain language summary
Intestinal permeability (IP) is dependent on the structure and function of the intestinal barrier. The gut barrier integrity is the result of ongoing equilibrium and crosstalk involving the microbiome, the mucus, the enterocytes [intestinal absorptive cells], the gut immune system, and the gut–vascular barrier. The main aim of this study was to explore the pan-enteric IP (stomach, small intestine, and colon) with respect to size and fat distribution, as well as the presence of liver steatosis. The study is a cohort study that examined 120 subjects (obese n = 45, overweight n=30, normal weight n = 45). Groups were gender-matched except for the prevalence of males in the overweight group. Results highlight the existence of an association between colonic (but not stomach and small intestinal) permeability, obesity, and liver steatosis. Findings show that: - liver steatosis was detected in 69 (57.5%) subjects, of which 36 (52%) were males. The prevalence of liver steatosis increased from 4% in normal weight subjects to 77%, and to 98% in overweight and obese subjects, respectively. - gastrointestinal permeability changed between age groups at every tract, whereas stomach and small intestine IP decreased with age. Furthermore, this finding also occurred in subjects aged over or equal to 65 years, with respect to colonic permeability. Authors conclude that further studies must evaluate the possibility of modulating colonic permeability to allow both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.
Abstract
Intestinal permeability (IP) is essential in maintaining gut-metabolic functions in health. An unequivocal evaluation of IP, as marker of intestinal barrier integrity, however, is missing in health and in several diseases. We aimed to assess IP in the whole gastrointestinal tract according to body mass index (BMI) and liver steatosis. In 120 patients (61F:59M; mean age 45 ± SEM 1.2 years, range: 18-75), IP was distinctively studied by urine recovery of orally administered sucrose (SO, stomach), lactulose/mannitol ratio (LA/MA, small intestine), and sucralose (SA, colon). By triple quadrupole mass-spectrometry and high-performance liquid chromatography, we measured urinary recovery of saccharide probes. Subjects were stratified according to BMI as normal weight, overweight, and obesity, and answered questionnaires regarding dietary habits and adherence to the Mediterranean Diet. Liver steatosis was assessed by ultrasonography. IP at every gastrointestinal tract was similar in both sexes and decreased with age. Stomach and small intestinal permeability did not differ according to BMI. Colonic permeability increased with BMI, waist, neck, and hip circumferences and was significantly higher in obese than in lean subjects. As determined by logistic regression, the odds ratio (OR) of BMI increment was significantly higher in subjects in the highest tertile of sucralose excretion, also after adjusting for age and consumption of junk food. The presence of liver steatosis was associated with increased colonic permeability. Patients with lower score of adherence to Mediterranean diet had a higher score of 'junk food'. Intestinal permeability tended to increase in subjects with a lower adherence to Mediterranean diet. In conclusion, colonic (but not stomach and small intestinal) permeability seems to be linked to obesity and liver steatosis independently from dietary habits, age, and physical activity. The exact role of these last factors, however, requires specific studies focusing on intestinal permeability. Results should pave the way to both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.
-
5.
Relationship between vitamin D status and the vaginal microbiome during pregnancy.
Jefferson, KK, Parikh, HI, Garcia, EM, Edwards, DJ, Serrano, MG, Hewison, M, Shary, JR, Powell, AM, Hollis, BW, Fettweis, JM, et al
Journal of perinatology : official journal of the California Perinatal Association. 2019;39(6):824-836
-
-
-
Free full text
-
Plain language summary
The composition of the vaginal microflora can significantly impact both reproductive and neonatal health. Numerous studies support the important role for sufficient serum or plasma concentrations of 25-hydroxy vitamin D (25(OH)D) during pregnancy in preventing negative outcomes. The study’s hypothesis was that vitamin D status is associated with the vaginal microbiome. This study is an analysis of a sub-cohort from a randomised, placebo-controlled clinical trial of vitamin D supplementation of pregnant women who were enrolled during the first trimester of pregnancy and followed until delivery. Participants (n=387) were randomised and received supplement: 191 received 400 IU (control group) and 196 received 4400 IU (treatment group). Results show that women in both the control and treatment groups displayed higher circulating 25(OH)D concentrations with increasing gestational age. Furthermore, among women of African ancestry, there was a negative correlation between 25(OH)D and abundance of Megasphaera [type of anaerobic microflora]. Authors conclude that certain vaginal bacteria are associated with plasma 25(OH)D concentration.
Abstract
OBJECTIVE Evidence supports an inverse association between vitamin D and bacterial vaginosis (BV) during pregnancy. Furthermore, both the vaginal microbiome and vitamin D status correlate with pregnancy outcome. Women of African ancestry are more likely to experience BV, to be vitamin D deficient, and to have certain pregnancy complications. We investigated the association between vitamin D status and the vaginal microbiome. STUDY DESIGN Subjects were assigned to a treatment (4400 IU) or a control group (400 IU vitamin D daily), sampled three times during pregnancy, and vaginal 16S rRNA gene taxonomic profiles and plasma 25-hydroxyvitamin D [25(OH)D] concentrations were examined. RESULT Gestational age and ethnicity were significantly associated with the microbiome. Megasphaera correlated negatively (p = 0.0187) with 25(OH)D among women of African ancestry. Among controls, women of European ancestry exhibited a positive correlation between plasma 25(OH)D and L. crispatus abundance. CONCLUSION Certain vaginal bacteria are associated with plasma 25(OH)D concentration.
-
6.
The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study.
Häger, J, Bang, H, Hagen, M, Frech, M, Träger, P, Sokolova, MV, Steffen, U, Tascilar, K, Sarter, K, Schett, G, et al
Nutrients. 2019;11(10)
-
-
-
Free full text
Plain language summary
Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory musculoskeletal disorder, affecting around 1% of the world population. Risk factors are genetic and environmental, with diet appearing to be an important environmental trigger. The impacts of diet on the gut microbiota are well studied, including the ability of the gut microbiome to manipulate the immune system. This small feasibility study of 36 patients with RA aimed to examine the effect of short-term high fibre dietary supplementation on T-reg cell numbers (cells which regulate the immune system). A high fibre bar was provided to study subjects for 28 days and measurements taken of immune and inflammation markers, bone erosion, gut bacterial changes and quality of life. The authors found a positive improvement to patient immune systems at the end of the intervention, as well as decreased markers of bone erosion. Physical functioning and quality of life were also reported as significantly improved. Whilst this is a small uncontrolled trial, the results support increasing the fibre intake when working with RA clients.
Abstract
Short-chain fatty acids are microbial metabolites that have been shown to be key regulators of the gut-joint axis in animal models. In humans, microbial dysbiosis was observed in rheumatoid arthritis (RA) patients as well as in those at-risk to develop RA, and is thought to be an environmental trigger for the development of clinical disease. At the same time, diet has a proven impact on maintaining intestinal microbial homeostasis. Given this association, we performed a feasibility study in RA patients using high-fiber dietary supplementation with the objective to restore microbial homeostasis and promote the secretion of beneficial immunomodulatory microbial metabolites. RA patients (n = 36) under routine care received daily high-fiber bars or cereals for 28 days. Clinical assessments and laboratory analysis of immune parameters in blood and stool samples from RA patients were done before and after the high-fiber dietary supplementation. We observed an increase in circulating regulatory T cell numbers, favorable Th1/Th17 ratios, as well as decreased markers of bone erosion in RA patients after 28 days of dietary intervention. Furthermore, patient-related outcomes of RA improved. Based on these results, we conclude that controlled clinical studies of high-fiber dietary interventions could be a viable approach to supplement or complement current pharmacological treatment strategies.
-
7.
Gut microbiota alterations associated with reduced bone mineral density in older adults.
Das, M, Cronin, O, Keohane, DM, Cormac, EM, Nugent, H, Nugent, M, Molloy, C, O'Toole, PW, Shanahan, F, Molloy, MG, et al
Rheumatology (Oxford, England). 2019;58(12):2295-2304
-
-
-
Free full text
-
Plain language summary
Osteoporosis, characterised by reduced bone density or ‘brittle bones’ affects a significant number of individuals over the age of 50 worldwide. Contributing factors include calcium and vitamin D deficiency and the presence of other inflammatory conditions. The composition of gut bacteria, the gut microbiome, plays an important role in immune activity and changes in composition have been associated with other inflammatory conditions. This cohort study of 181 individuals at high risk of reduced bone density and fractures, aimed to determine whether different gut microbiota composition is associated with bone density. Dexa scans and faecal samples were used as part of the assessment and confounding factors of diet, BMI, supplementation and medication were included in the analysis. The authors of the study found 6 species of gut bacteria that were significantly altered in numbers in the groups with osteoporosis and osteopenia, after controlling for confounding factors, and suggest that they could be used as markers of disease risk or progression and as a therapeutic target. Nutrition Practitioners working with bone density can focus on supporting the gut microbiome as part of their nutrition protocols.
Abstract
OBJECTIVE To investigate compositional differences in the gut microbiota associated with bone homeostasis and fractures in a cohort of older adults. METHODS Faecal microbiota profiles were determined from 181 individuals with osteopenia (n = 61) or osteoporosis (n = 60), and an age- and gender-matched group with normal BMD (n = 60). Analysis of the 16S (V3-V4 region) amplicon dataset classified to the genus level was used to identify significantly differentially abundant taxa. Adjustments were made for potential confounding variables identified from the literature using several statistical models. RESULTS We identified six genera that were significantly altered in abundance in the osteoporosis or osteopenic groups compared with age- and gender-matched controls. A detailed study of microbiota associations with meta-data variables that included BMI, health status, diet and medication revealed that these meta-data explained 15-17% of the variance within the microbiota dataset. BMD measurements were significantly associated with alterations in the microbiota. After controlling for known biological confounders, five of the six taxa remained significant. Overall microbiota alpha diversity did not correlate to BMD in this study. CONCLUSION Reduced BMD in osteopenia and osteoporosis is associated with an altered microbiota. These alterations may be useful as biomarkers or therapeutic targets in individuals at high risk of reductions in BMD. These observations will lead to a better understanding of the relationship between the microbiota and bone homeostasis.
-
8.
Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.
Roager, HM, Vogt, JK, Kristensen, M, Hansen, LBS, Ibrügger, S, Mærkedahl, RB, Bahl, MI, Lind, MV, Nielsen, RL, Frøkiær, H, et al
Gut. 2019;68(1):83-93
-
-
-
Free full text
-
Plain language summary
Whole grain consumption has been linked with decreased risk of lifestyle-related diseases. While animal studies have shown the gut microbiome to be a mediator of metabolic health, human studies examining the effect of whole grain intake of the gut remain inconclusive. The aim of this study was to investigate the effects of a whole grain diet on the gut microbiome, gut functionality and biomarkers of metabolic health. In this randomised, controlled, crossover study, 50 participants completed two 8-week dietary intervention periods comprising of a whole grain diet and a refined grain diet with a 6-week washout period. Examinations were done at the beginning and end of each intervention period to assess anthropometry and various plasma and gut markers. This study found that a whole grain diet as compared with a refined grain diet reduced energy intake and body weight as well as circulating markers of inflammation. Contrary to the hypothesis, these benefits were all observed independent of changes in the gut microbiome. Based on these results, the authors conclude higher intake of whole grains should be recommended to those at risk of inflammation-related disease.
Abstract
OBJECTIVE To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER NCT01731366; Results.