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Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis.Frontiers in Cellular and Infection... 2023Liver cirrhosis is the end stage of various chronic liver diseases (CLDs). The gut microbiota can impact the liver environment and trigger chronic liver inflammation...
BACKGROUND
Liver cirrhosis is the end stage of various chronic liver diseases (CLDs). The gut microbiota can impact the liver environment and trigger chronic liver inflammation through the gut-liver axis. Alteration of the gut microbiota has become an effective strategy in the biological treatment of cirrhosis.
METHODS
Twenty-eight patients with liver cirrhosis and 16 healthy individuals were included, and fresh stool samples were collected. We analyzed changes in the gut microbiota between groups by 16S rRNA sequencing and evaluated the association between microbiota alterations and hepatic function. Additionally, 102 cirrhotic patients were retrospectively enrolled and divided into a probiotic group (n=44) and a nonprobiotic group (n=58) in addition to standard treatment for cirrhosis. Patients were monitored for hematological parameters and hepatic function during the six-month follow-up.
RESULTS
The gut microbiota profile of patients with cirrhosis was greatly different from that of healthy individuals, presenting with significantly reduced α diversity and decreased abundance of representative SCFA-producing bacteria including , and . The pathogenic bacteria , , and were greatly enriched in cirrhotic patients. Additionally, patients with decompensated cirrhosis (DCPC) had a significantly reduced abundance of compared to compensated cirrhosis (CPC), which is also a SCFA-producing bacteria, and the lower to ratio and enhanced MDR values were also shown in DCPC patients compared to CPC patients. In addition, the abundance of was negatively related to hepatic function in cirrhotic patients, including the levels of ALT, AST, and DBIL. From the retrospective study, we found that biochemical improvements in alanine transaminase (ALT) and total bilirubin (TBIL) were obtained in DCPC patients who received oral probiotic therapy compared with the nonprobiotic group.
CONCLUSION
Severe microbial dysbiosis existed in patients with liver cirrhosis, especially patients who reached the decompensatory stage. SCFA-producing bacteria were significantly reduced in cirrhosis. Altered gut microbiota cause changes in functional modules, which may contribute to cirrhosis progression and are associated with clinical prognosis. Adjuvant probiotic supplementation to enhance SCFA-producing bacteria can be a prospective therapy for patients with cirrhosis.
Topics: Humans; Gastrointestinal Microbiome; Retrospective Studies; RNA, Ribosomal, 16S; Liver Cirrhosis; Bacteria; Probiotics
PubMed: 37483387
DOI: 10.3389/fcimb.2023.1218552 -
Gut Microbes 2024Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic (BL)... (Randomized Controlled Trial)
Randomized Controlled Trial
Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to investigate the biochemical pathways underlying the beneficial effects of BL NCC3001 using metabolomic profiling. Patients received probiotic (1x 10CFU, n=16) or placebo (n=19) daily for 6 weeks. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Brain activity in response to negative emotional stimuli was assessed by functional Magnetic Resonance Imaging. Probiotic fecal abundance was quantified by qPCR. Quantitative measurement of specific panels of plasma host-microbial metabolites was performed by mass spectrometry-based metabolomics. Probiotic abundance in feces was associated with improvements in anxiety and depression scores, and a decrease in amygdala activation. The probiotic treatment increased the levels of butyric acid, tryptophan, N-acetyl tryptophan, glycine-conjugated bile acids, and free fatty acids. Butyric acid concentration correlated with lower anxiety and depression scores, and decreased amygdala activation. Furthermore, butyric acid concentration correlated with the probiotic abundance in feces. In patients with non-constipation IBS, improvements in psychological comorbidities and brain emotional reactivity were associated with an increased abundance of BL NCC3001 in feces and specific plasma metabolites, mainly butyric acid. These findings suggest the importance of a probiotic to thrive in the gut and highlight butyric acid as a potential biochemical marker linking microbial metabolism with beneficial effects on the gut-brain axis.
Topics: Irritable Bowel Syndrome; Humans; Probiotics; Metabolome; Male; Adult; Female; Feces; Middle Aged; Depression; Anxiety; Bifidobacterium longum; Gastrointestinal Microbiome; Metabolomics; Comorbidity
PubMed: 38717445
DOI: 10.1080/19490976.2024.2347715 -
Cells Nov 2023Obesity and Western-like diet consumption leads to gut microbiome dysbiosis, which is associated with the development of cardio-metabolic diseases and poor health...
Obesity and Western-like diet consumption leads to gut microbiome dysbiosis, which is associated with the development of cardio-metabolic diseases and poor health outcomes. The objective of this study was to reduce Western diet-mediated gut microbial dysbiosis, metabolic dysfunction, and systemic inflammation through the administration of a novel combined intervention strategy (oral probiotic bacteria supplements and muscadine grape extract (MGE)). To do so, adult female C57BL/6 mice were fed a low-fat control or Western-style diet and sub-grouped into diet alone, probiotic intervention, antibiotic treatments, MGE supplementation, a combination of MGE and probiotics, or MGE and antibiotics for 13 weeks. Mouse body weight, visceral adipose tissue (VAT), liver, and mammary glands (MG) were weighed at the end of the study. Fecal 16S rRNA sequencing was performed to determine gut bacterial microbiome populations. Collagen, macrophage, and monocyte chemoattractant protein-1 (MCP-1) in the VAT and MG tissue were examined by immunohistochemistry. Adipocyte diameter was measured in VAT. Immunohistochemistry of intestinal segments was used to examine villi length, muscularis thickness, and goblet cell numbers. We show that dietary interventions in Western diet-fed mice modulated % body weight gain, visceral adiposity, MG weight, gut microbial populations, and inflammation. Intervention strategies in both diets effectively reduced VAT and MG fibrosis, VAT and MG macrophages, adipocyte diameter, and VAT and MG MCP-1. Interventions also improved intestinal health parameters. In conclusion, dietary intervention with MGE and probiotics modulates several microbial, inflammatory, and metabolic factors reducing poor health outcomes associated with Western diet intake.
Topics: Female; Animals; Mice; Gastrointestinal Microbiome; Vitis; Dysbiosis; RNA, Ribosomal, 16S; Diet, High-Fat; Mice, Inbred C57BL; Obesity; Probiotics; Inflammation
PubMed: 37998334
DOI: 10.3390/cells12222599 -
Trials Oct 2023Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females characterized by ovulatory dysfunction, hyperandrogenism, and other metabolic...
The effects of intermittent fasting diet alone or in combination with probiotic supplementation in comparison with calorie-restricted diet on metabolic and hormonal profile in patients with polycystic ovary syndrome: study protocol for a randomized clinical trial.
INTRODUCTION
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females characterized by ovulatory dysfunction, hyperandrogenism, and other metabolic disorders. Both intermittent fasting and specific probiotics have been suggested to help improve patients with PCOS through changes in gut microbial composition, circadian clock, and metabolic regulation. Therefore, the present study aims to investigate the effects of intermittent fasting alone or in combination with probiotic supplementation compared to the calorie-restricted (CR) diet on anthropometric measures, metabolic status, inflammation, and oxidative stress in women with PCOS.
METHODS
We will carry out a randomized clinical trial for 8 weeks. Participants will be randomly assigned (1:1:1) to one of the three groups: (1) a 14:10 early time-restricted feeding (TRF) diet with probiotic supplementation (n = 30); (2) a 14:10 early TRF diet with placebo supplementation (n = 30); (3) a CR diet (energy-restricted 25% of required calories) with placebo supplementation as a control group (n = 30). The primary outcomes will be changes in body weight and insulin resistance. However, glycemic control, lipid profile, metabolic parameters, sex hormone-binding globulin, dehydroepiandrosterone, anti-Mullerian hormone, free androgen index, hirsutism, acne, antioxidant and oxidant status, inflammation, anthropometric measures, mental health, sleep quality, appetite, eating behavior, food craving, and blood pressure are secondary outcomes. All outcomes of this study will be evaluated in pre- and post-intervention.
DISCUSSION
We hypothesized that 10-h TRE administered alone or in combination with probiotic supplementation to overweight and obese PCOS subjects would lead to weight loss and improved metabolic, hormonal, inflammatory, and antioxidant markers compared to control subjects following a standard 3-meal-per-day CR diet.
ETHICAL ASPECTS
The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1401.425).
TRIAL REGISTRATION
Iranian Registry of Clinical Trials IRCT20121110011421N5. Registered on 3 October 2022.
Topics: Humans; Female; Polycystic Ovary Syndrome; Antioxidants; Iran; Intermittent Fasting; Diet; Probiotics; Inflammation; Randomized Controlled Trials as Topic
PubMed: 37880791
DOI: 10.1186/s13063-023-07691-5 -
Current Rheumatology Reports Dec 2023This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible... (Review)
Review
PURPOSE OF REVIEW
This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives.
RECENT FINDINGS
The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.
Topics: Humans; Lipopolysaccharides; Osteoarthritis; Pain; Probiotics; Arthralgia
PubMed: 37656392
DOI: 10.1007/s11926-023-01108-7 -
Scientific Reports Oct 2023The aim was to assess the weight-reducing effects of various doses of a probiotic dietary supplement and evaluate the tolerance and safety of increased dosage. A 3-month... (Randomized Controlled Trial)
Randomized Controlled Trial
The aim was to assess the weight-reducing effects of various doses of a probiotic dietary supplement and evaluate the tolerance and safety of increased dosage. A 3-month double-blinded, randomized, placebo-controlled trial, followed by a 3-month open phase, was conducted at Karolinska Institutet, Sweden. The probiotic compound AB001 was tested at two doses (single and double) and compared with placebo during the blinded phase, and at triple dose during the open phase. Eighty-one volunteers, 18-45 years old, with overweight were included. The primary outcome was change in weight. Secondary outcomes were changes in; BMI, waist circumference, blood pressure, blood lipids, glucose metabolism, liver enzymes, vitamin levels, and bowel habits. After 3 months (n = 81), no difference in weight, BMI, waist circumference, blood pressure, or biomarkers were observed between the groups. Forty-five individuals continued with triple dose. The group with initial single dose decreased 0.93 ± 4.73 kg (p = 0.34), and the group with double dose initially decreased 1.93 ± 3.70 kg (p = 0.027). Reported changes in bowel habits and gastro-intestinal problems were similar for all doses. The results indicate that a long-term use of at least double dose AB001 may be more beneficial for weight loss than lower doses. However, in the double blinded phase, no differences between groups were found. The probiotic compound AB001 was well tolerated and can safely be used up to double dose for 90 days followed by triple dose for 90 days.Trial registration: Clinicaltrial.gov NCT04897698, registered on 21 May 2021.
Topics: Humans; Adult; Adolescent; Young Adult; Middle Aged; Overweight; Weight Loss; Probiotics; Dietary Supplements; Biomarkers; Double-Blind Method
PubMed: 37875559
DOI: 10.1038/s41598-023-45395-7 -
Gut Microbes Dec 2023Several probiotic-derived factors have been identified as effectors of probiotics for exerting beneficial effects on the host. However, there is a paucity of studies to...
Several probiotic-derived factors have been identified as effectors of probiotics for exerting beneficial effects on the host. However, there is a paucity of studies to elucidate mechanisms of their functions. p40, a secretory protein, is originally isolated from a probiotic bacterium, GG. Thus, this study aimed to apply structure-functional analysis to define the functional peptide of p40 that modulates the epigenetic program in intestinal epithelial cells for sustained prevention of colitis. analysis revealed that p40 is composed of a signal peptide (1-28 residues) followed by a coiled-coil domain with uncharacterized function on the N-terminus, a linker region, and a β-sheet domain with high homology to CHAP on the C-terminus. Based on the p40 three-dimensional structure model, two recombinant p40 peptides were generated, p40N120 (28-120 residues) and p40N180 (28-180 residues) that contain first two and first three coiled coils, respectively. Compared to full-length p40 (p40F) and p40N180, p40N120 showed similar or higher effects on up-regulating expression of (encoding a methyltransferase), promoting mono- and trimethylation of histone 3 on lysine 4 (H3K4me1/3), and enhancing gene expression and protein production that leads to SMAD2 phosphorylation in human colonoids and a mouse colonic epithelial cell line. Furthermore, supplementation with p40F and p40N120 in early life increased H3K4me1, expression and differentiation of regulatory T cells (Tregs) in the colon, and mitigated disruption of epithelial barrier and inflammation induced by DSS in adult mice. This study reveals the structural feature of p40 and identifies a functional peptide of p40 that could maintain intestinal homeostasis.
Topics: Adult; Humans; Animals; Mice; Bacterial Proteins; Gastrointestinal Microbiome; Peptides; Colitis; Probiotics
PubMed: 37815528
DOI: 10.1080/19490976.2023.2264456 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024The prevalence of childhood and adolescent obesity has globally reached alarming dimensions and many adolescents affected by obesity already present one or more... (Review)
Review
The prevalence of childhood and adolescent obesity has globally reached alarming dimensions and many adolescents affected by obesity already present one or more obesity-related comorbidities. In recent years, emerging evidence supporting the role of gut microbiota in the pathophysiology of metabolic diseases has been reported and the use of prebiotics, probiotics, synbiotics and postbiotics as a strategy to manipulate gut microbiota has become popular. The aim of this review is to explore the relationship between gut microbiota and metabolic syndrome in adolescents and to discuss the potential use of prebiotics, probiotics, synbiotics and postbiotics for the prevention and treatment of this clinical picture in adolescence. According to the most recent literature, prebiotics, probiotics and synbiotics have no clear effect on MetS, but a possible modulation of anthropometric parameters has been observed after synbiotic supplementation. Only one study has examined the role of postbiotics in alleviating metabolic complications in children with obesity but not in adolescents. More extensive research is needed to support the conclusions drawn so far and to develop effective microbiome-based interventions that may help improving the quality of life of children and adolescents exposed to the increasing prevalence of MetS.
Topics: Humans; Metabolic Syndrome; Prebiotics; Probiotics; Synbiotics; Adolescent; Gastrointestinal Microbiome; Pediatric Obesity; Child
PubMed: 38704983
DOI: 10.1016/j.clnu.2024.04.032 -
Protein & Cell Nov 2023Microbes are commonly sensitive to shifts in the physiological and pathological state of their hosts, including mothers and babies. From this perspective, the microbiome... (Review)
Review
Microbes are commonly sensitive to shifts in the physiological and pathological state of their hosts, including mothers and babies. From this perspective, the microbiome may be a good indicator for diseases during pregnancy and has the potential to be used for perinatal health monitoring. This is embodied in the application of microbiome from multi body sites for auxiliary diagnosis, early prediction, prolonged monitoring, and retrospective diagnosis of pregnancy and infant complications, as well as nutrition management and health products developments of mothers and babies. Here we summarized the progress in these areas and explained that the microbiome of different body sites is sensitive to different diseases and their microbial biomarkers may overlap between each other, thus we need to make a diagnosis prudently for those diseases. Based on the microbiome variances and additional anthropometric and physical data, individualized responses of mothers and neonates to meals and probiotics/prebiotics were predictable, which is of importance for precise nutrition and probiotics/prebiotics managements and developments. Although a great deal of encouraging performance was manifested in previous studies, the efficacy could be further improved by combining multi-aspect data such as multi-omics and time series analysis in the future. This review reconceptualizes maternal and infant health from a microbiome perspective, and the knowledge in it may inspire the development of new options for the prevention and treatment of adverse pregnancy outcomes and bring a leap forward in perinatal health care.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Microbiota; Probiotics; Retrospective Studies
PubMed: 37184065
DOI: 10.1093/procel/pwad029 -
Phytomedicine : International Journal... Dec 2023Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and...
Fermentation of Ganoderma lucidum and Raphani Semen with a probiotic mixture attenuates cyclophosphamide-induced immunosuppression through microbiota-dependent or -independent regulation of intestinal mucosal barrier and immune responses.
BACKGROUND
Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system.
PURPOSE
We established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms.
METHODS
First, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied.
RESULTS
Probiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier.
CONCLUSION
This is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.
Topics: Animals; Mice; Reishi; Fermentation; Probiotics; Cyclophosphamide; Gastrointestinal Microbiome; Immunity; Immunosuppression Therapy; Seeds
PubMed: 37722243
DOI: 10.1016/j.phymed.2023.155082