The effect of synbiotics in the treatment of drug-resistant epilepsy and the parental burden of caregivers: a single-arm pretest-posttest trial.

BACKGROUND: In patients with drug-resistant epilepsy (DRE), the composition of the gut microbiome changes compared to drug-sensitive patients and healthy individuals. Synbiotics, a mixture of probiotics and prebiotics, aim to improve the balance of bacteria in the gut microbiome. This study aimed to assess the effect of synbiotics on the treatment of DRE and the burden on caregivers. METHODS: This one-group pretest-posttest quasi-experimental study was conducted in Arak, Iran. Thirty children with DRE, diagnosed by a pediatric neurologist and meeting the inclusion criteria in 2021-22, were included in the study. In addition to anticonvulsant drugs, infants were administered PediLact at a dose of 5-15 drops per day for eight weeks, and KidiLact at a dose of one sachet per day for eight weeks for children aged 2-15 years. Both PediLact and KidiLact are synbiotics. To investigate the burden on caregivers (parents), the Zarit Caregiver Burden Interview was conducted. In addition, the number of epileptic seizures was assessed from mothers before and immediately after the intervention over one month. RESULTS: The mean age of the participants in the study was 8.6 years (SD: 3.4). Eighteen participants (60%) were boys, and 12 (40%) were girls. The results of the study showed a statistically significant decrease in the mean burden on caregivers, from 34.20 (SD: 14.4) before the intervention to 30.26 (SD: 15.8) after the intervention (P = 0.017). The mean frequency of seizures decreased significantly, from 15.83 (SD: 12.9) before the intervention to 12.73 (SD: 12.8) after the intervention (P = 0.001). Following the intervention, the seizure frequency stopped in two patients, decreased by 50% in six patients, increased in one patient, and remained unchanged in 21 patients. CONCLUSION: The results suggest that Symbiotics in DRE patients are associated with a lower parental burden of caregivers and seizure frequency. Well-designed randomized clinical trial studies are recommended to generate rigorous causal evidence and conclusions.

Synbiotic supplementation may globally improve non-motor symptoms in patients with stable Parkinson's disease: results from an open label single-arm study.

Gut microbiota changes and brain-gut-axis (BGA) dysregulation are common in people with Parkinson's Disease (PD). Probiotics and prebiotics are emerging as a potential therapeutic approach for PD patients. The aim of this paper was to assess the neurological and gastroenterological effects in PD patients with constipation after the administration of a synbiotic product, with a focus on behavioral and cognitive symptoms. We enrolled patients with stable PD who met diagnostic criteria for functional constipation and/or irritable bowel syndrome with constipation according to Rome IV Criteria. Patients received a synbiotic treatment (Enterolactis Duo, containing the probiotic strain Lacticaseibacillus paracasei DG and the prebiotic fiber inulin) for 12 weeks. A neurological and a gastroenterological evaluation were collected before and after the treatment. In addition, 16S rRNA gene profiling and short chain fatty acid quantification were performed to characterize the microbial ecosystem of fecal samples collected before (n = 22) and after (n = 9) the synbiotic administration. 30 patients were consecutively enrolled. After treatment, patients performed better in MDS-UPDRS part 1 (p = 0.000), SCOPA-AUT (p = 0.001), TAS-20 (p = 0.014), HAM-D (p = 0.026), DIFt (p = 0.003), PAS-A (p = 0.048). Gastroenterological evaluations showed improvements in PAC-SYM score (p < 0.001), number of complete bowel movement (p < 0.001) and BSFS (p < 0.001). After the synbiotic administration, we observed a significant increase in the abundance of the order Oscillospirales, as well as the Oscillospiraceae family and the species Faecalibacterium prausnitzii within this order in fecal samples. Synbiotic treatment demonstrates potential efficacy in ameliorating non-motor features in PD patients.

A Synbiotic Combining Chitin-Glucan and Lactobacillus acidophilus NCFM Induces a Colonic Molecular Signature Soothing Intestinal Pain and Inflammation in an Animal Model of IBS.

Chitin-glucan (CG) is a new generation of prebiotic. Lactobacillus acidophilus NCFM® (NCFM) is a probiotic with the ability to decrease abdominal pain. We evaluate the functional and molecular gastrointestinal responses to a synbiotic administration combining CG and NCFM in a rat model of long-lasting colon hypersensitivity. The intracolonic pressure was assessed during the 9-week experiment in animals receiving CG in association or not with NCFM and compared to that in Lacticaseibacillus paracasei Lpc-37®-treated animals and control rats receiving tap water. The effects of the synbiotic were evaluated using the Wallace score, the quantification of colon myeloperoxidase (MPO) and the master genes driving analgesia and inflammation. CG 1.5 alone and NCFM 109 colony forming units (CFU) alone similarly decreased the visceral pain sensitivity. Lpc-37 had no significant effect. The best profile of pain perception inhibition was obtained with the combination of CG 1.5 g and NCFM 109 CFU, confirming a synbiotic property. This synbiotic treatment significantly reduced macroscopic colonic lesions and MPO concentrations, and induced master genes involved in analgesia (CB1, CB2, MOR, PPARα), with a downregulation of inflammatory cytokines (IL-1ß, TNFα) and an induction of IL-10 and PPARγ. In conclusion, CG 1.5 g + NCFM 109 CFU significantly decreased visceral pain perception and intestinal inflammation through the regulation of master genes.

Investigating the effect of synbiotic supplementation on inflammatory indices in critically ill septic children: a protocol study for randomized control trial.

BACKGROUND: Sepsis, a severe inflammatory response to infection, is a global health priority due to its high mortality and long-term disability rates. Its pathophysiology involves both inflammation and immune suppression. Managing sepsis requires significant healthcare resources and expenditure, with sepsis being a leading cause of hospital costs. Gut microbiotas play a crucial role in sepsis, and probiotics show promise in managing it by restoring microbial balance. Despite advances, targeted therapies for sepsis remain elusive, necessitating innovative approaches such as probiotic therapy. METHOD: Fifty-four eligible patients with sepsis will be randomly assigned to either the synbiotic or placebo group. The synbiotic supplement, KidiLact, comprises ten probiotic strains and prebiotic fructooligosaccharides. Participants will receive two sachets daily for 7 days, mixed with sterile water and administered orally or via gavage. Inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) will be evaluated. Anthropometric measurements, nutritional assessment, biochemical analysis, and clinical evaluation will be conducted to assess treatment outcomes. Statistical analysis will be performed to compare results between the two groups, employing SPSS version 19 with a significance level of P < .05. CONCLUSION: This randomized clinical trial aims to evaluate synbiotic supplementation effects on inflammatory markers and clinical outcomes in pediatric sepsis patients in the pediatric intensive care unit (PICU). Probiotics have shown promise in reducing proinflammatory cytokines like IL-6, TNF-α, and CRP, which are vital in the inflammatory response. Synbiotics can enhance gut integrity, preventing pathogen translocation and reducing inflammation. If our expectations regarding the effects of probiotics are correct, we can use them as a cost-effective supplement to improve the condition of pediatric sepsis in hospitals. TRIAL REGISTRATION: IRCT,IRCT20230523058266N1 Registered 30 October 2023, https://irct.behdasht.gov.ir/trial/71397 .

Effects of synbiotic supplementation on the components of metabolic syndrome in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Antipsychotic drugs may have adverse effects on the components of metabolic syndrome. Previous studies have shown that changes in the intestinal microbiome are associated with metabolic disturbances in patients with schizophrenia. The objective of this study was to determine the effects of synbiotics on the components of metabolic syndrome as primary outcomes in patients with schizophrenia. Secondary outcomes were HbA1c, insulin resistance, LDL-c, and anthropometric measurements. METHODS: In this double-blind, placebo-controlled trial, seventy patients with schizophrenia receiving antipsychotic drugs who had at least two criteria of metabolic syndrome were randomly divided into two groups to receive either two capsules of a synbiotic supplement or a placebo daily for 8 weeks. Anthropometric indices and biochemical parameters were measured at baseline and after the intervention. RESULTS: Fifty-five patients completed the study. The synbiotic supplement significantly decreased waist circumference and HbA1C compared to placebo (-2.66 ± 4.20 vs. 3.03 ± 4.50 and - 0.26 ± 0.54 vs. 0.20 ± 0.75, respectively). Although BMI did not change significantly in the synbiotic + antipsychotic group, it increased in the placebo + antipsychotic group (-0.37 ± 1.00 vs. 0.61 ± 1.09 P < 0.5). LDL-c and triglyceride (TG) levels decreased significantly in the synbiotic + antipsychotic group, but the change was not significantly different from that of the placebo + antipsychotic group. FBS, HDL-c, systolic and diastolic blood pressure, insulin resistance, and total cholesterol were not significantly different between the two groups after intervention. CONCLUSION: Synbiotic supplement may decrease waist circumference, HbA1c, LDL and TG and prevent BMI increase in patients receiving antipsychotic drugs. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT Number: IRCT20090901002394N45), Date: 26-12-2019.

Synbiotics in patients at risk for spontaneous preterm birth: protocol for a multi-centre, double-blind, randomised placebo-controlled trial (PRIORI).

BACKGROUND: Prematurity remains one of the main causes of neonatal morbidity and mortality. Approximately two thirds of preterm births are spontaneous, i.e. secondary to preterm labour, preterm prelabour rupture of membranes (PPROM) or cervical insufficiency. Etiologically, the vaginal microbiome plays an important role in spontaneous preterm birth (sPTB). Vaginal dysbiosis and bacterial vaginosis are well-known risk factors for ascending lower genital tract infections and sPTB, while a Lactobacillus crispatus-dominated vaginal microbiome is associated with term deliveries. Synbiotics may help to achieve and/or maintain a normal, Lactobacillus-dominated vaginal microbiome. METHODS: We will perform a multi-centre, double-blind, randomised, placebo-controlled trial. Women aged 18 years or older with a singleton pregnancy are eligible for inclusion at 80/7-106/7 weeks gestational age if they have one or more of the following risk factors for sPTB: previous sPTB at 240/7-356/7 weeks, prior PPROM before 360/7 weeks, or spontaneous pregnancy loss at 140/7-236/7 weeks of gestation. Exclusion criteria are multiple gestation, cervix conisation, inflammatory bowel disease, uterine anomaly, and the use of pro-/pre-/synbiotics. Patients will be randomised to oral synbiotics or placebo, starting before 11 weeks of gestation until delivery. The oral synbiotic consists of eight Lactobacillus species (including L. crispatus) and prebiotics. The primary outcome is the gestational age at delivery. Vaginal microbiome analysis once per trimester (at approximately 9, 20, and 30 weeks) and delivery will be performed using metataxonomic sequencing (16S rRNA gene) and microbial culture. Secondary outcomes include PPROM, the use of antibiotics, antenatal admission information, and neonatal outcomes. DISCUSSION: This study will evaluate the effect of oral synbiotics on the vaginal microbiome during pregnancy in a high-risk population and correlate the microbial changes with the gestational age at delivery and relevant pregnancy outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05966649. Registered on April 5, 2024.

Assessment of the Prophylactic Effects of Probiotics, Prebiotics, and Synbiotics Against COVID-19 Infection: A Systematic Review of Randomized Controlled Trials.

Background: Although various treatments are developed against COVID-19 variants, probiotic, and synbiotic adjunct therapy with several benefits such as safety, low cost, and availability could be needed for preventing or treating COVID-19 infection.Objective: The present systematic review aimed to assess the prophylactic efficacy of the probiotic, prebiotic, and synbiotic administration against COVID-19.Methods: The protocol of this systematic review was registered at the PROSPERO (Code number: CRD42023418900). The Scopus, Cochrane Library, Web of Sciences, and PubMed databases were systematically searched to define the clinical trials published up to November 2022 in the English language. The comparison of the incidence of COVID-19 disease and levels of specific antibodies against SARS-cov2 between the intervention and placebo groups were evaluated in this systematic review.Results: According to the five included trials, four indicated the incidence of COVID-19, and no significant differences were observed between the probiotic and placebo groups during 1, 2, or 3 months of follow-up in the mentioned studies. Regarding the antibody assays against SARS-Cov2 including IgM, IgG, or IgA reported by three eligible trials, there were no significant differences between the intervention and control groups.Conclusion: It seems that the administration of single or multi-strain probiotics or synbiotics had no prophylactic effects in different populations such as high-risk staff exposed to COVID-19, elderly nursing home residents, healthy adults, and household contact with COVID-19 patients during 1-to-3-months of intervention.

Effects of synbiotics on necrotizing enterocolitis and full enteral feeding in very low birth weight infants: A double-blind, randomized controlled trial.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial disease primarily affecting infants with very low birth weight (VLBW). Research has shown that the pathogenesis of NEC is associated with abnormal bacterial colonization. Synbiotics, dietary supplements containing probiotics (beneficial bacteria) and prebiotics (non-digestible food), can alter the gut microbiome. METHODS: A double-blind, randomized controlled trial was conducted to assess the efficacy of PediLact®, an oral drop multi-strain synbiotic containing Lactobacillus rhamnosus, Lactobacillus reuteri, and Bifidobacterium infantis, on nutritional parameters and the occurrence of NEC in VLBW neonates. In this study, 118 VLBW neonates from neonatal intensive care units were randomly allocated in a 1:1 ratio to receive either a synbiotic or a placebo. The synbiotic administration continued until the infant was fully fed. The primary outcomes were the occurrence of NEC and the number of days required to achieve full enteral feeding. Log-binomial regression and ANOVA/ANCOVA models were used for analysis. RESULTS: In the group that received the synbiotic, the incidence of NEC decreased significantly (adjusted RR = 0.22, 95% CI: 0.07-0.72, P value = .01; adjusted RD = -0.22, 95% CI: -0.33 to -0.12, P value < .001; NNT = 5). Additionally, feeding intolerance was less frequent in this group (adjusted RR = 0.27, 95% CI: 0.14-0.51, P value < .001; NNT = 3). Furthermore, consumption of the synbiotic was associated with significant weight gain (approximately 40 g) in infants (adjusted SMD = 0.63; 95% CI: 0.26-1.00, P value < .001). The duration of hospitalization and the time required to reach full enteral feeding were also significantly shorter in the synbiotic group (by approximately 3 days). No serious side effects were reported. CONCLUSION: Prescribing multi-strain synbiotics reduces the incidence of NEC in VLBW infants and has beneficial effects on breastfeeding tolerance and weight gain velocity. Therefore, physicians may consider prescribing synbiotics to VLBW neonates.

Probiotics/prebiotics/synbiotics and human neuropsychiatric outcomes: an umbrella review.

The neuropsychiatric effects of probiotics, prebiotics, and synbiotics have been gaining attention since the rise of microbial-gut-brain axis research. Nevertheless, some of the findings are inconsistent, and few studies have analysed the similarities and differences in the neuropsychiatric effects of the three comprehensively. To reveal the respective neuropsychiatric effects of probiotics, prebiotics, and synbiotics and synthesise the similarities and differences among the three effects, 47 meta-analyses with 12 types of neuropsychiatric results were integrated under an umbrella review. Probiotics, prebiotics, and synbiotics intake might all be associated with improvements in some neuropsychiatric outcomes, including neuropsychological test outcomes (probiotic and prebiotic), hepatic encephalopathy outcomes (probiotic, prebiotic, and synbiotic), instant memory in patients with Alzheimer's disease (probiotic), depressive symptoms (probiotic, prebiotic and synbiotic), mood states and psychiatric distress (probiotic), overall mental health (probiotic), neurological function (probiotic), brain-derived neurotrophic factor (BDNF) concentration (probiotic and synbiotic), and Pittsburgh Sleep Quality Index (PSQI) score (probiotic). All three are similar in that the intake of probiotics, prebiotics, and synbiotics might be associated with improvements in hepatic encephalopathy outcomes and depressive symptoms, both probiotic and synbiotic intake might be associated with elevated BDNF concentrations, and both probiotic and prebiotic intake might be associated with improved neuropsychological test results. The difference between the three is that the neuropsychiatric effects of probiotics might be more widespread and be reflected in the fact that probiotic intake might also be associated with improvements in mood states and psychiatric distress, overall mental health, neurological function, Alzheimer's disease patients' instant memory, and PSQI score. Probiotics might be the best and most promising option for improving neuropsychiatric outcomes. In the future, in addition to requiring more high-quality meta-analyses, further preclinical studies are needed to explore specific relevant mechanisms and determine true causal relationships.

Exploring the synergistic effects of vitamin D and synbiotics on cytokines profile, and treatment response in breast cancer: a pilot randomized clinical trial.

This study was designed to investigate the effect of vitamin D and/or synbiotics on the response to treatment, cytokines profile and hormonal biomarkers in breast cancer patients undergoing neoadjuvant therapy. A total of 76 patients were recruited and completed the course of the intervention between 2019 and 2021 in Kerman, Iran. breast cancer patients were randomly enrolled in this study. Patients divided into four groups to receive one of the following regimens: placebo, vitamin D, synbiotics and a combination of vitamin D and synbiotics. clinicopathologic parameters, inflammatory and anti-inflammatory biomarkers and hormonal levels were measured at the baseline and four months after intervention. The study results found no clear link between the interventions and achieving pathological complete response (pCR), and a similar trend was observed in Ki-67 index examination. After neoadjuvant therapy, TNF-α concentrations decreased, with vitamin D supplementation moderating this decline. Vitamin D supplemented groups showed a significant increase in serum IL-6 levels. While IL-10 levels decreased in the placebo group, all intervention groups were protected from this decline. Moreover, there was a notable increase in the anti-inflammatory index, particularly in the group receiving both vitamin D and synbiotic supplementation, suggesting potential synergistic anti-inflammatory effects from their combined administration. The outcomes suggest a potential anti-inflammatory function of this combination. Consequently, more extensive studies with prolonged follow-up periods and substantial sample sizes are warranted to thoroughly evaluate their potential benefits for breast cancer patients.

Evaluation of the synbiotic effects of Saccharomyces cerevisiae and mushroom extract on the growth performance, digestive enzyme activity, and immune status of zebrafish danio rerio.

BACKGROUND: The quest for candidate probiotics and prebiotics to develop novel synbiotics for sustainable and profitable fish farming remains a major focus for various stakeholders. In this study, we examined the effects of combining two fungal probiotics, Saccharomyces cerevisiae and Aspergillus niger with extracts of Jerusalem artichoke and white button mushroom to develop a synbiotic formulation to improve the growth and health status of zebrafish (Danio rerio). An initial in vitro study determined the most effective synbiotic combination, which was then tested in a 60-day in vivo nutritional trial using zebrafish (80 ± 1.0 mg) as a model animal. Four experimental diets were prepared: a control diet (basal diet), a prebiotic diet with 100% selected mushroom extract, a probiotic diet with 107 CFU of S. cerevisiae/g of diet, and a synbiotic diet with 107 CFU of S. cerevisiae/g of diet and 100% mushroom extract. As readouts, growth performance, survival, digestive enzyme activity and innate immune responses were evaluated. RESULTS: In vitro results showed that the S. cerevisiae cultured in a medium containing 100% mushroom extract exhibited the maximum specific growth rate and shortest doubling time. In the in vivo test with zebrafish, feeding them with a synbiotic diet, developed with S. cerevisiae and mushroom extract, led to a significant improvement in the growth performance of zebrafish (P < 0.05). The group of zebrafish fed with the synbiotic diet showed significantly higher levels of digestive enzyme activity and immune responses compared to the control group (P < 0.05). CONCLUSION: Taken together, these results indicated that the combination of S. cerevisiae and mushroom extract forms an effective synbiotic, capable of enhancing growth performance and immune response in zebrafish.

Meta-analysis of randomized controlled trials of the effects of synbiotics, probiotics, or prebiotics in controlling glucose homeostasis in non-alcoholic fatty liver disease patients.

Background: Probiotics, prebiotics, and synbiotics have been suggested as a possible therapy for non-alcoholic fatty liver disease (NAFLD). However, their efficacy in improving blood glucose levels in NAFLD patients remains uncertain. Objective: The aim of this study was to assess the effects of supplementation with probiotics, prebiotics, or synbiotics on fasting blood glucose (FBG) levels in NAFLD patients. Methods: We searched PubMed, Web of Science, and Google Scholar for relevant trials published up to March 2024. Out of 3369 identified studies, 24 randomized controlled trials (RCTs) were included. Results: Probiotic, prebiotic, or synbiotic supplementation substantially reduced FBG (n = 23; standard mean difference (SMD) = -0.17; 95% confidence interval (CI): -0.30, -0.03; P = 0.02), fasting insulin levels (n = 12; SMD = -0.28; 95% CI: -0.49, -0.07; P = 0.01), and homeostatic model assessment for insulin resistance (HOMA-IR; n = 14; SMD = -0.28; 95% CI: -0.47, -0.09; P = 0.004). However, glycosylated hemoglobin (HbA1c; n = 3; SMD = -0.17; 95% CI: -0.48, 0.13; P = 0.27) was not significantly affected. The FBG-decreasing effect diminished as the body mass index (BMI) of volunteers increased in the baseline. Additionally, the number of probiotic strains and geographic region were shown to significantly affect FBG levels. Conclusion: This meta-analysis indicates that supplementation with probiotics, prebiotics, or synbiotics may aid in controlling glucose homeostasis in patients with NAFLD.

The effect of synbiotics on liver enzymes, obesity indices, blood pressure, lipid profile, and inflammation in patients with non-alcoholic fatty liver: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) benefit from using synbiotics. However, findings from existing trials remain contentious. Therefore, this meta-analysis evaluated the effects of synbiotics on liver enzymes, blood pressure, inflammation, and lipid profiles in patients with NAFLD. METHODS: We searched PubMed, Embase, Cochrane, Scopus, and Web of Science for randomized controlled trials (RCTs) regarding synbiotics supplementation in patients with NAFLD. RESULTS: The meta-analysis revealed that synbiotics supplementation significantly improved liver enzymes (AST, WMD: -9.12 IU/L; 95 % CI: -13.19 to -5.05; ALT, WMD: -8.53 IU/L; 95 % CI: -15.07 to -1.99; GGT, WMD: -10.42 IU/L; 95 % CI: -15.19 to -5.65), lipid profile (TC, WMD: -7.74 mg/dL; 95 % CI: -12.56 to -2.92), obesity indices (body weight, WMD: -1.95 kg; 95 % CI: -3.69 to -0.22; WC, WMD: -1.40 cm; 95 % CI: -2.71 to -0.10), systolic blood pressure (SBP, WMD: -6.00 mmHg; 95 % CI: -11.52 to -0.49), and inflammatory markers (CRP, WMD: -0.69 mg/L; 95 % CI: -1.17 to -0.21; TNF-α, WMD: -14.01 pg/mL; 95 % CI: -21.81 to -6.20). CONCLUSION: Overall, supplementation with synbiotics positively improved liver enzymes, obesity indices, and inflammatory cytokines in patients with NAFLD.

Combining Bifidobacterium longum subsp. infantis and human milk oligosaccharides synergistically increases short chain fatty acid production ex vivo.

To enhance health benefits, a probiotic can be co-administered with a metabolizable prebiotic forming a synergistic synbiotic. We assessed the synergies resulting from combining Bifidobacterium longum subsp. infantis LMG 11588 and an age-adapted blend of six human milk oligosaccharides (HMOs) in ex vivo colonic incubation bioreactors seeded with fecal background microbiota from infant and toddler donors. When HMOs were combined with B. infantis LMG 11588, they were rapidly and completely consumed. This resulted in increased short chain fatty acid (SCFA) production compared to the summed SCFA production from individual ingredients (synergy). Remarkably, HMOs were partially consumed for specific infant donors in the absence of B. infantis LMG 11588, yet all donors showed increased SCFA production upon B. infantis LMG 11588 supplementation. We found specific bacterial taxa associated with the differential response pattern to HMOs. Our study shows the importance of carefully selecting pre- and probiotic into a synergistic synbiotic that could benefit infants.

Using Synbiotics as a Therapy to Protect Mental Health in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurological disorder that represents a major cause of dementia worldwide. Its pathogenesis involves multiple pathways, including the amyloid cascade, tau protein, oxidative stress, and metal ion dysregulation. Recent studies have suggested a critical link between changes in gut microbial diversity and the disruption of the gut-brain axis in AD. Previous studies primarily explored the potential benefits of probiotics and prebiotics in managing AD. However, studies have yet to fully describe a novel promising approach involving the use of synbiotics, which include a combination of active probiotics and new-generation prebiotics. Synbiotics show potential for mitigating the onset and progression of AD, thereby offering a holistic approach to address the multifaceted nature of AD. This review article primarily aims to gain further insights into the mechanisms of AD, specifically the intricate interaction between gut bacteria and the brain via the gut-brain axis. By understanding this relationship, we can identify potential targets for intervention and therapeutic strategies to combat AD effectively. This review also discusses substantial evidence supporting the role of synbiotics as a promising AD treatment that surpasses traditional probiotic or prebiotic interventions. We find that synbiotics may be used not only to address cognitive decline but also to reduce AD-related psychological burden, thus enhancing the overall quality of life of patients with AD.

Faecalibacterium prausnitzii, FOS and GOS loaded synbiotic reverses treatment-resistant depression in rats: Restoration of gut-brain crosstalk.

Alterations in commensal gut microbiota, such as butyrate-producing bacteria and its metabolites, have been linked to stress-related brain disorders, including depression. Herein, we investigated the effect of Faecalibacterium prausnitzii (ATCC-27766) administered along with fructooligosaccharides (FOS) and galactooligosaccharides (GOS) in a rat model of treatment-resistant depression (TRD). The behavioral changes related to anxiety-, anhedonia- and despair-like phenotypes were recorded employing elevated plus maze, sucrose-preference test, and forced-swim test, respectively. Rats exposed to unpredictable chronic mild-stress (UCMS) and adrenocorticotropic hormone (ACTH) injections exhibited a TRD-like phenotype. Six-week administration of F. prausnitzii and FOS + GOS ameliorated TRD-like conditions in rats. This synbiotic treatment also restored the decreased levels of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate in the fecal samples of TRD rats. Synbiotic-recipient TRD rats displayed an increased abundance of Lactobacillus helveticus, Lactobacillus hamsteri, and Ruminococcus flavefaciens. Moreover, more mucus-producing goblet cells were seen in the colon of synbiotic-treated rats, suggesting improved gut health. The synbiotic treatment effectively modulated neuroinflammation by reducing proinflammatory cytokines (IFN-γ, TNF-α, CRP, and IL-6). It normalized the altered levels of key neurotransmitters such as serotonin, gamma-aminobutyric acid, noradrenaline, and dopamine in the hippocampus and/or frontal cortex. The enhanced expression of brain-derived neurotrophic factor, tryptophan hydroxylase 1, and serotonin transporter-3 (SERT-3), and reduced levels of indoleamine 2,3-dioxygenase 1 (IDO-1) and kynurenine metabolite were observed in the synbiotic-treated group. We suggest that F. prausnitzii and FOS + GOS-loaded synbiotic may reverse the TRD-like symptoms in rats by positively impacting gut health, neuroinflammation, neurotransmitters, and gut microbial composition.

Effect of biotic supplementation on infant sleep and settling behaviours: A systematic review and meta-analysis.

Microbiota changes throughout infancy and can be modified by biotic supplementation, which includes probiotics, prebiotics, synbiotics, and post-biotics. Given the potential influence of the microbiome on infant sleep, this systematic review and meta-analysis aimed to determine the effect of biotic supplementation on sleep behaviours in full-term infants aged 0-12 months. In June 2023, we searched seven databases for randomised controlled trials (RCTs) of biotic supplementation intervention studies using synonymous terms for 'infant' AND 'biotic' AND 'sleep' (PROSPERO registration ID: CRD42022358822). Title/abstracts and the full texts were independently screened. Data on infant sleep and settling behaviour outcomes, reported adverse/side effects, and co-morbid conditions were extracted for analysis. Using the modified Cochrane Collaboration tool, two independent reviewers judged the risk of bias. Meta-analyses were conducted using RevMan5. Our search yielded 453 unique studies and 23 RCTs are included in this review. Probiotic supplementation was the most common biotic supplementation (provided in 53% of studies), while 28% and 19% offered prebiotic and synbiotic supplementation, respectively. Sleep duration was the most common (95%) reported outcome for probiotics. No significant differences were reported in sleep duration during the 1st to 4th week of probiotic supplementation. However, in the 5th week of probiotic supplementation, infants who received placebo slept significantly longer (MD = -35.17 min, 95% CI [-69.72, -0.62]), suggesting a borderline significance that is clinically relevant. There were limited studies and timeframe alignment to analyse prebiotics, synbiotics, post-biotics, and para-probiotics effects on infant sleep duration. The study suggests probiotic supplementation does not increase infant sleep duration within the first 4 postpartum weeks and may contribute to reduced sleep duration in the fifth week. Limited studies were available to assess the effects of biotic supplementation over the first 12 postpartum months. Future research should assess the full range of sleep behaviours, infant feeding type, and microbiome.

Clostridium tyrobutyricum in Combination with Chito-oligosaccharides Modulate Inflammation and Gut Microbiota for Inflammatory Bowel Disease Treatment.

Synbiotics, the combination of probiotics and prebiotics, are thought to be a pragmatic approach for the treatment of various diseases, including inflammatory bowel disease (IBD). The synergistic therapeutic effects of probiotics and prebiotics remain underexplored. Clostridium tyrobutyricum, a short-chain fatty acid (SCFA) producer, has been recognized as a promising probiotic candidate that can offer health benefits. In this study, the treatment effects of synbiotics containing C. tyrobutyricum and chitooligosaccharides (COSs) on IBD were evaluated. The results indicated that the synbiotic supplement effectively relieved inflammation and restored intestinal barrier function. Additionally, the synbiotic supplement could contribute to the elimination of reactive oxygen species (ROS) and improve the production of SCFAs through the SCFAs-producer of C. tyrobutyricum. Furthermore, such the synbiotic could also regulate the composition of gut microbiota. These findings underscore the potential of C. tyrobutyricum and COSs as valuable living biotherapeutics for the treatment of intestinal-related diseases.

The impact of synbiotic on serum sCD163/sTWEAK, paraoxonase 1, and lipoproteins in patients with chronic heart failure: a randomized, triple-blind, controlled trial.

Cardiovascular disease is one of the leading causes of death worldwide. Evidence suggests that alterations in the gut microbiome could play a role in cardiovascular diseases, including heart failure. The purpose of this study was to evaluate the effect of synbiotics on serum paraoxonase 1(PON1), soluble CD163/soluble TNF-like weak inducer of apoptosis (sCD163/sTWEAK), and lipid profile, which are involved in heart failure in patients with chronic heart failure. In this triple-blind randomized clinical trial, 90 eligible patients were included in the study. They were randomly assigned to receive one capsule (500 mg) of synbiotics or a placebo daily for ten weeks. Serum PON1, sCD163/sTWEAK, and lipid profiles were measured at the beginning and end of the study. The data were analyzed by SPSS 24, and the p-value < 0.05 was considered statistically significant. Among 90 patients who met the inclusion criteria, 80 completed the study. The primary outcomes showed a small effect on sTWEAK, with an adjusted standard mean difference (SMD) of 0.2. However, no significant changes were observed in sCD163/sTWEAK (SMD: 0.16). Secondary outcomes indicated no changes in PON1, total cholesterol (TC), or LDL-C levels. However, there was an increase in HDL-C levels (adjusted SMD: 0.46, 95% CI: 0.02-0.91) and a decrease in TG and TC/HDL levels (adjusted SMD: - 0.5 and - 0.3, respectively) in the synbiotic group. A favorable effect of synbiotics on sTWEAK, HDL, TG, and TC/HDL of patients with heart failure was observed, but no statistically significant effect was found on sCD163/sTWEAK, PON1, LDL, and TC factors.

Postbiotics as Adjuvant Therapy in Cancer Care.

Postbiotics are defined as a preparation of inanimate microorganisms and/or their components that confers a health benefit to the host. They range from cell wall fragments to metabolites, bacterial lysates, extracellular vesicles, and short-chain fatty acids (SCFAs). Postbiotics may influence carcinogenesis via a variety of mechanisms. They can promote homeostatic immune responses, reduce inflammation, induce selective cytotoxicity against tumor cells, as well as the enabling the control of tumor cell proliferation and enhancing intestinal epithelial barrier function. Therefore, probiotics can serve as an adjunct strategy in anticancer treatment together with chemotherapy and immunotherapy. Up to now, the only relevant postbiotics used as interventions in oncological patients remain vitamin K molecules, with few phase-II and III trials available. In fact, postbiotics' levels are strictly dependent on the gut microbiota's composition, which may vary between individuals and can be altered under different physiological and pathological conditions. Therefore, the lack of consistent clinical evidence supporting postbiotics' efficacy is due to their poor bioavailability, short half-life, and fluctuating levels. Synbiotics, a mixture of prebiotics and probiotics, are expected to have a more homogeneous bioavailability with respect to postbiotics and may have greater potential for future development. In this review, we focus on the role of postbiotics as an adjuvant therapy in cancer treatment.