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Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.
Lai, H, Li, Y, He, Y, Chen, F, Mi, B, Li, J, Xie, J, Ma, G, Yang, J, Xu, K, et al
Gut microbes. 2023;15(1):2197837
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Functional constipation is characterised by continuously difficult, incomplete, or infrequent defecation, without an organic origin. Effective intervention strategies are required to relieve the functional constipation difficulties, particularly in rapidly aging populations, such as Chinese populations. The aim of this study was to evaluate the effectiveness of three dietary fibre formulas (polydextrose, psyllium husk, and wheat bran + psyllium husk) and one probiotic supplement on the improvement of constipation symptoms among Chinese adults with functional constipation. This study was a double-blinded randomised placebo-controlled trial which enrolled 250 participants who were randomly assigned to one of the five groups. Results showed: - that daily supplement of three prebiotic formulas with dietary fibres, or a probiotic formula effectively relieved hard stool in functional constipation patients after 4 weeks intervention. - the capacity of gut microbial genera in shaping the intervention responsiveness in the improvement of bowel movement frequency, Bristol stool scale score, and degree of defecation straining. Authors conclude that the pre or probiotic interventions may modulate gut microbiota, associated with intestinal health.
Abstract
Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884. What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber – gut microbiota (Anaerostipes)—constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.
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Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.
Wang, H, Ma, C, Li, Y, Zhang, L, A, L, Yang, C, Zhao, F, Han, H, Shang, D, Yang, F, et al
Microbiology spectrum. 2023;11(3):e0444022
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A long-term high-fat diet will not only disrupt the balance of lipid metabolism in the body and cause metabolic disorders but also lead to chronic diseases, such as hyperlipidaemia, type 2 diabetes, hypertension, and obesity. Hyperlipidaemia is also an important contributing factor in cardiovascular disease. The aim of this study was to analyse the effects of a mixed probiotic formulation on hyperlipidaemia, with focus on changes in patients’ gut microbiota and their metabolic potential. This study was a 3-month randomised controlled intervention trial. A total of 56 hyperlipidaemic patients were recruited and randomised into either the placebo or probiotic (receiving a mixed probiotic formulation) group. Results show that the intake of the probiotic mix effectively reduced the serum levels of total cholesterol and low-density lipoprotein cholesterol, while increasing serum high-density lipoprotein cholesterol levels, in patients with hyperlipidaemia. In fact, there was a strong association between the desirable changes in patients’ lifestyle habits and lowering of these indexes. Furthermore, although insignificant changes were observed in the lipid metabolome and gut microbiota structure, some interesting fecal bacteria and blood metabolites increased significantly after Probio-X intervention. Authors conclude that their findings show that probiotic administration is a promising approach in managing hyperlipidaemia and improving public health.
Abstract
Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.
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Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study.
Wang, S, Ren, H, Zhong, H, Zhao, X, Li, C, Ma, J, Gu, X, Xue, Y, Huang, S, Yang, J, et al
Gut microbes. 2022;14(1):2003176
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Hyperlipidaemia is a major risk factor for atherosclerotic cardiovascular diseases particularly when combined with hyperglycaemia and type 2 diabetes (T2D). Current diagnostic criteria and treatment targets are based on evaluating fasting lipidaemia (FL). However, increasing evidence has supported that a high level of non-fasting lipidaemia, mainly constituted by post-prandial lipidaemia (PL), is also an important CVD risk factor. The aim of this study was to investigate how the combination treatment of berberine (BBR) and probiotics (Prob), or either one could exert benefit on lowering PL, and whether their impact on gut microbiota could contribute to this effect. This study is based on the PREMOTE trial, which was a randomised, double-blind, placebo-controlled clinical trial in 20 medical centres in China and enrolled newly diagnosed T2D patients. This lipidomic study included 365 of the 409 participants enrolled for the PREMOTE trial. Results showed that: - Prob+BBR combined therapy exerted a similar effect on reducing fasting lipidaemia with BBR alone but a superior effect on the levels of postprandial plasma total cholesterol and post-prandial low-density lipoprotein cholesterol compared to either BBR or Prob alone. - a substantial decrease in various lipid species after Prob+BBR treatment. Authors conclude that their findings proved the therapeutic effect of a combined treatment of oral administration of probiotics with berberine on improving PL in patients newly diagnosed with T2D and proposed a new gut microbiome related remedy for managing dyslipidaemia, covering both PL and FL, in patients with T2D.
Abstract
Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob (B. breve) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.
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Effect of Lactobacillus casei on lipid metabolism and intestinal microflora in patients with alcoholic liver injury.
Li, X, Liu, Y, Guo, X, Ma, Y, Zhang, H, Liang, H
European journal of clinical nutrition. 2021;75(8):1227-1236
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Alcoholic liver disease (ALD) is a series of liver diseases caused by long-term heavy drinking. Lipid metabolism disorder often occurs in people with alcoholic liver injury. Treatment is mainly a combination of alcohol abstinence, improving nutrition, treating the liver injury, and preventing or reversing the progress of liver fibrosis or promoting liver regeneration. The aim of this study was to investigate the effect of Lactobacillus casei on lipid metabolism and intestinal microflora in patients with alcoholic liver injury. This study was a randomised, double-blind, placebo-controlled trial. A total of 181 ALD patients were recruited and randomly assigned to one of the three groups; low-dose group, high-dose group and positive control group (+ there was another group of 20 healthy people which served as normal control group). Results showed disorder of lipid metabolism, intestinal flora imbalance and inflammation in patients with alcoholic liver injury. Furthermore, after supplementation of Lactobacillus casei, there was a significant increase in the amount of Lactobacillus and Bifidobacterium. Authors conclude that Lactobacillus casei supplementation can improve lipid metabolism and regulate intestinal flora disorders in patients with alcoholic liver injury.
Abstract
BACKGROUND The present study aims to investigate the effect of Lactobacillus casei on lipid metabolism and intestinal microflora in patients with alcoholic liver injury. METHODS In a double-blind randomized controlled trial, 158 recruited alcoholic liver injury patients were randomized to three treatments for 60 days: low-dose group (LP, n = 58, 100 ml of Lactobacillus casei strain Shirota (LcS)), high-dose group (HP, n = 54, 200 ml of LcS), and positive control group (PC, n = 46, 100 ml of special drinks without active Lactobacillus casei). Another group of 20 healthy people was served as normal control group (NC). RESULTS The serum levels of TG and LDLC in the HP group were significantly decreased by 26.56% and 23.83%, respectively than those in the PC group (P < 0.05). After supplementation of Lactobacillus casei, there was a significant increase in the amount of Lactobacillus and Bifidobacterium when compared with the PC group (P < 0.05). CONCLUSIONS Supplementation of Lactobacillus casei can improve lipid metabolism and regulate intestinal flora disorders in patients with alcoholic liver injury.
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Functional interactions between the gut microbiota and host metabolism.
Tremaroli, V, Bäckhed, F
Nature. 2012;489(7415):242-9
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This literature review aims to discuss evidence for the role of the gut microbiota in metabolism and possible links to obesity. Obesity and caloric intake can influence the microbiota, but whether the reverse is true in humans remains unclear. Much of the mechanisms have been determined in rodents, determining similar pathways in humans is difficult. The interplay of diet, host and gut microbiota may cause increased gut permeability (leaky gut) that could lead to an increase in inflammation that may cause obesity, fatty liver disease and insulin resistance. It is increasingly accepted that gut microbiota can contribute to diseases such as obesity, diabetes and cardiovascular disease, but exactly how and by how much remains unclear. Evidence for treating the microbiota to help with these metabolic diseases, either by pre- or probiotic supplementation, is building. However, double-blind, placebo-controlled studies are required to determine effects. The influence of the gut microbiota is a promising area, but one that needs further research.
Abstract
The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease.