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Synbiotics may be useful to mitigate intestinal diseases such as ulcerative colitis. Here we show that combining 13'-carboxychromanol (δT3-13'), a metabolite of vitamin E δ-tocotrienol (δT3) via omega-oxidation, and Lactococcus lactis subsp. cremori (L. cremoris), but neither agent alone, significantly attenuated dextran sulfate sodium (DSS)-induced fecal bleeding and diarrhea, histologic colitis and interleukin 1β in mice. The combination of δT3-13'+L. cremoris also synergistically prevented DSS-caused compositional changes in gut microbiota and enriched beneficial bacteria including Lactococcus and Butyricicoccus. Interestingly, the anti-colitis effect correlated with the concentrations of δT3-13'-hydrogenated metabolite that contains 2 double bonds on the side chain (δT2-13'), instead of δT3-13' itself. Moreover, in contrast to δT3-13', combining δT3 and L. cremoris showed modest anti-colitis effects and did not prevent colitis-associated dysbiosis. In addition, ex vivo anaerobic incubation studies revealed that gut microbes selected by δT3-13' in the animal study could metabolize this compound to δT2-13' via hydrogenation, which appeared to be enhanced by L. cremoris. Overall, our study demonstrates that combining δT3-13' and L. cremoris can synergically prevent dysbiosis, and may be a novel synbiotic against colitis potentially via promoting δT3-13' metabolizers, which in turn contributes to superior beneficial effects of the combination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/objectives: Correction of decreased diversity of the gut microbiome, which is characteristic of menopause, by supplementation with a synbiotic may attenuate or prevent dysbiosis processes and preserve bone mass. We describe the rationale and design of the OsteoPreP trial aimed at evaluating the effects of 12 months of supplementation with a synbiotic on bone and metabolic health in postmenopausal Caucasian women., Methods: This is a randomized, double-blinded, placebo-controlled trial among 160 Caucasian, postmenopausal women with no current diagnosis of osteoporosis or supplementation with pro- or prebiotics, and no medical treatment affecting bone turnover. Dual-energy X-ray absorptiometry scans will be conducted at screening to confirm absence of osteoporosis. The primary outcome is the relative change (%) in total bone mineral density of the distal tibia at 12 months post-treatment between the active and placebo groups, as determined via high-resolution peripheral quantitative computed tomography. Secondary outcomes are the effects on immune system modulation and cognition, gut microbiota composition, and musculoskeletal and metabolic functions, with particular emphasis on blood glucose regulation., Conclusions: The trial will inform on the efficacy and safety of a synbiotic containing both aerobic and anerobic bacterial strains and a prebiotic fiber on reduction in bone loss and on indices of blood glucose regulation. This trial may pave the way for an exciting field of translational research and be the underpinnings of the prevention strategy of osteoporosis and the management of metabolic dysfunction in postmenopausal women. The trial is registered with clinicaltrials.gov (NCT05348694).

The global epidemic of type 2 diabetes mellitus (T2DM) imposes a substantial burden on public health and healthcare expenditures, thereby driving the pursuit of cost-effective preventive and therapeutic strategies. Emerging evidence suggests a potential association between dysbiosis of gut microbiota and its metabolites with T2DM, indicating that targeted interventions aimed at modulating gut microbiota may represent a promising therapeutic approach for the management of T2DM. In this review, we concentrated on the multifaceted interactions between the gut microbiota and the intestinal barrier in the context of T2DM. We systematically summarized that the imbalance of beneficial gut microbiota and its metabolites may constitute a viable therapeutic approach for the management of T2DM. Meanwhile, the mechanisms by which gut microbiota interventions, such as probiotics, prebiotics, postbiotics, and synbiotics, synergistically improve insulin resistance in T2DM are summarized. These mechanisms include the restoration of gut microbiota structure, upregulation of intestinal epithelial cell proliferation and differentiation, enhancement of tight junction protein expression, promotion of mucin secretion by goblet cells, and the immunosuppressive functions of regulatory T cells (Treg) and M2 macrophages. Collectively, these actions contribute to the amelioration of the body's metabolic inflammatory status. Our objective is to furnish evidence that supports the clinical application of probiotics, prebiotics, and postbiotics in the management of T2DM., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer remains a global problem, with millions of new cases diagnosed yearly and countless lives lost. The financial burden of cancer therapy, along with worries about the long-term safety of existing medicines, necessitates the investigation of alternative approaches to cancer prevention. Probiotics generate chemopreventive compounds such as bacteriocins, short-chain fatty acids (SCFA), and extracellular polymeric substances (EPS), which have demonstrated the ability to impede cancer cell proliferation, induce apoptosis, and bolster the expression of pro-apoptotic genes. On the other hand, prebiotics, classified as non-digestible food ingredients, promote the proliferation of probiotics within the colon, thereby ensuring sustained functionality of the gut microbiota. Consequently, the synergistic effect of combining prebiotics with probiotics, known as the synbiotic effect, in dietary interventions holds promise for potentially mitigating cancer risk and augmenting preventive measures. The utilization of gut microbiota in cancer treatment has shown promise in alleviating adverse health effects. This review explored the potential and the role of probiotics and synbiotics in enhancing health and contributing to cancer prevention efforts. In this review, the applications of functional probiotics and synbiotics, the mechanisms of action of probiotics in cancer, and the relationship of probiotics with various drugs were discussed, shedding light on the potential of probiotics and synbiotics to alleviate the burdens of cancer treatment., Competing Interests: Declarations Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Human milk contains an abundance of nutrients which benefit the development and growth of infants. However, infant formula has to be used when breastfeeding is not possible. The large differences between human milk and infant formula in prebiotics lead to the suboptimal intestinal health of infant formula-fed infants. This functional deficit of infant formula may be overcome through other dietary polysaccharides that have been characterized. The aim of this review was to summarize the potential applications of dietary polysaccharides as prebiotics, synbiotics, and postbiotics in infant formula to better mimic the functionality of human milk prebiotics for infant gut health. Previous studies have demonstrated the influences of dietary polysaccharides on gut microbiota, SCFA production, and immune system development. Compared to prebiotics, synbiotics and postbiotics showed better application potential in shaping the gut microbiota, the prevention of pathogen infections, and the development of the immune system. Moreover, the safety issues for biotics still require more clinical trials with a large-scale population and long time duration, and the generally accepted regulations are important to regulate related products. Pectin polysaccharides has similar impacts to human milk oligosaccharides on gut microbiota and the repairing of a damaged gut barrier, with similar functions also being observed for inulin and β-glucan. Prebiotics as an encapsulation material combined with probiotics and postbiotics showed better potential applications compared to traditional material in infant formula.

The human gastrointestinal tract contains trillions of microbes that affect the body. Dysbiosis in the composition of gut microbiota is one of the leading causes of chronic inflammatory diseases such as inflammatory bowel disease (IBD). IBD is a global public health challenge and millions of people in the world are suffering from this disease. It is a recurring inflammatory disease that affects different parts of the human digestive system. Ulcerative colitis and Crohn's disease are the two main types of IBD with similar clinical symptoms. The increasing incidence and severity of IBD require new treatment methods. The composition of the gut microbiota can be modified using dietary supplements such as prebiotics and bacterial supplements called probiotics. Furthermore, the effects of the microbiome can be improved by using paraprobiotics (non-viable, inactivated bacteria or their components) and/or postbiotics (products of bacterial metabolism)., Competing Interests: Declarations. Competing Interests: The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The trillions of microbes that constitute the human gut microbiome play a crucial role in digestive health, immune response regulation, and psychological wellness. Maintaining gut microbiota is essential as metabolic diseases are associated with it. Functional food ingredients potentially improving gut health include prebiotics, probiotics, synbiotics, and postbiotics (PPSPs). While probiotics are living bacteria that provide health advantages when ingested sufficiently, prebiotics are non-digestible carbohydrates that support good gut bacteria. Synbiotics work together to improve immunity and intestinal health by combining probiotics and prebiotics. Postbiotics have also demonstrated numerous health advantages, such as bioactive molecules created during probiotic fermentation. According to a recent study, PPSPs can regulate the synthesis of metabolites, improve the integrity of the intestinal barrier, and change the gut microbiota composition to control metabolic illnesses. Additionally, the use of fecal microbiota transplantation (FMT) highlights the potential for restoring gut health through microbiota modulation, reinforcing the benefits of PPSPs in enhancing overall well-being. Research has shown that PPSPs provide several health benefits, such as improved immunological function, alleviation of symptoms associated with irritable bowel disease (IBD), decreased severity of allergies, and antibacterial and anti-inflammatory effects. Despite encouraging results, many unanswered questions remain about the scope of PPSPs' health advantages. Extensive research is required to fully realize the potential of these functional food components in enhancing human health and well-being. Effective therapeutic and prophylactic measures require further investigation into the roles of PPSPs, specifically their immune-system-modulating, cholesterol-lowering, antioxidant, and anti-inflammatory characteristics.

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., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest.We confirmed that all authors have read and approved the manuscript. We further confirm that all authors have approved the order of authors listed in the manuscript.We understand that the Corresponding Author is the sole contact for the Editorial process. He is responsible for communicating with another author about progress, submission of revisions, and final approval of proofs., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hyperglycaemia, hyperlipidaemia, hypertension and obesity are the main risk factors affecting the development and prognosis of ischaemic heart disease, which is still an important cause of death today. In our study, male Sprague-Dawley rats were fed either a standard diet (SD) or a high fat and high carbohydrate diet (HF-HCD) for 8 weeks and streptozotocin (STZ) was injected at the seventh week of the feeding period. In one set of rats, a mixture of a prebiotic and probiotics (synbiotic, SYN) was administered by gavage starting from the beginning of the feeding period. Experimental myocardial ischaemia-reperfusion (30 min/60 min) was induced at the end of 8 weeks. Hyperglycaemia, hypertension and increased serum low-density lipoprotein levels occurred in SD- and HF-HCD-fed and STZ-treated rats followed for 8 weeks. Increased density of the Proteobacteria phylum was observed in rats with increased blood glucose levels, indicating intestinal dysbiosis. The severity of cardiac damage was highest in the dysbiotic HF-HCD-fed hyperglycaemic rats, which was evident with increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumour necrosis factor-α, and interleukin-6 levels, along with a decrease in ST-segment resolution index. SYN supplementation to either a normal or a high-fat high-carbohydrate diet improved gut dysbiosis, reduced anxiety, decreased CK-MB and cTnI levels, and alleviated myocardial ischaemia-reperfusion injury in hyperglycaemic rats., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background/objectives: Diet is one of the major determinants of the composition and function of the gut microbiome, and diverse studies have established directional connections between gut microbiome dysbiosis and skin dyshomeostasis. Furthermore, a significant link between the gut and certain skin-related disorders has been reported. This work reviews the mechanisms underlying the relationship between nutritional factors, gut microbiome, and certain skin diseases such as acne vulgaris, alopecia, and atopic dermatitis. In addition, it explores how the modulation of the gut microbiome and human skin through diet and various microbial strategies, including probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, may serve as future treatments for skin diseases, possibly replacing traditional methods such as antibiotic, topical corticosteroid, and laser therapies., Results: The adequate intake of certain foods can promote a balanced gut microbiome, potentially reducing skin inflammation and improving overall skin health, while poor dietary choices may lead to worse outcomes by disrupting gut homeostasis. In this regard, diets high in antioxidants, fiber, and phytonutrients appear to be beneficial for enhancing skin health and preventing associated comorbidities. In addition, the administration of probiotics, synbiotics, and postbiotics in the treatment of cutaneous diseases has been shown to restore skin dyshomeostasis and to improve the symptoms of the reviewed skin conditions., Conclusions: Consuming a healthy, plant-based diet can reduce skin inflammation and enhance overall skin health. Although the application of probiotics, synbiotics, and postbiotics has demonstrated promise in modulating inflammation, enhancing tissue regeneration, and inhibiting pathogenic colonization, further research is required.

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., (© 2024. The Author(s).)

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.

Alzheimer's disease (AD) is a complex neurodegenerative condition with growing evidence implicating the gut microbiota in its pathogenesis. This study aimed to investigate the effects of NMN synbiotics, a combination of β-nicotinamide mononucleotide (NMN), Lactobacillus plantarum, and lactulose, on the gut microbiota composition and metabolic profiles in APP/PS1 transgenic mice. Results demonstrated that NMN synbiotics led to a notable restructuring of the gut microbiota, with a decreased Firmicutes/Bacteroidetes ratio in the AD mice, suggesting a potential amelioration of gut dysbiosis. Alpha diversity indices indicated a reduction in microbial diversity following NMN synbiotics supplementation, while beta diversity analyses revealed a shift towards a more balanced microbial community structure. Functional predictions based on the 16S rRNA data highlighted alterations in metabolic pathways, particularly those related to amino acid and energy metabolism, which are crucial for neuronal health. The metabolomic analysis uncovered a significant impact of NMN synbiotics on the gut metabolome, with normalization of metabolic composition in AD mice. Differential metabolite functions were enriched in pathways associated with neurotransmitter synthesis and energy metabolism, pointing to the potential therapeutic effects of NMN synbiotics in modulating the gut-brain axis and synaptic function in AD. Immunohistochemical staining observed a significant reduction of amyloid plaques formed by Aβ deposition in the brain of AD mice after NMN synbiotics intervention. The findings underscore the potential of using synbiotics to ameliorate the neurodegenerative processes associated with Alzheimer's disease, opening new avenues for therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is constantly rising globally. There are barely any effective medications or supplements for the management of MASLD. We aim to systematically evaluate the most current evidence for gut microbiota-regulating supplements in patients with MASLD., Methods: We searched multiple electronic data for randomized controlled trials (RCTs) published from January 1, 2012, to July 15, 2023. The intervention measures included probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The control group was treated with a placebo or usual care. The intervention duration was divided into two periods (>12 weeks and ≤12 weeks). Adequate evaluation data for antibiotics and FMT have not been obtained. Therefore, the other three microbiota regulators are the primary evaluation measures in this study., Results: We found that probiotics alone could not improve clinical indicators in MASLD patients. However, synbiotics exhibited an improvement in reducing liver steatosis, TNF-ɑ levels, and increasing HDL-c levels, and the inflammatory markers of liver cells (ALT and AST) were also improved. For the effective intervention duration, this systematic review suggested that around 12 weeks is an ideal intervention cycle for MASLD patients., Conclusions: This meta-analysis supported the modulation of gut microbiota with synbiotics in the management of MASLD., Competing Interests: Declaration of competing interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Recent burgeoning literature unveils the importance of gut microbiota in the neuropathology of post-stroke brain injury and recovery. Indeed, ingestion of prebiotics/probiotics imparts positive effects on post-stroke brain injury, neuroinflammation, gut dysbiosis, and intestinal integrity. However, information on the disease-specific preference of selective prebiotics/probiotics/synbiotics and their underlying mechanism is yet elusive. Herein, we examined the effect of a new synbiotic formulation containing multistrain probiotics (Lactobacillus reuteri UBLRu-87, Lactobacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58, Lactobacillus salivarius UBLS-22, and Bifidobacterium breve UBBr-01), and prebiotic fructooligosaccharides using a middle cerebral artery occlusion (MCAO) model of cerebral ischemia in female and male rats. Three weeks pre-MCAO administration of synbiotic rescinded the MCAO-induced sensorimotor and motor deficits on day 3 post-stroke in rotarod, foot-fault, adhesive removal, and paw whisker test. We also observed a decrease in infarct volume and neuronal death in the ipsilateral hemisphere of synbiotic-treated MCAO rats. The synbiotic treatment also reversed the elevated levels/mRNA expression of the glial fibrillary acidic protein (GFAP), NeuN, IL-1β, TNF-α, IL-6, matrix metalloproteinase-9, and caspase-3 and decreased levels of occludin and zonula occludens-1 in MCAO rats. 16S rRNA gene-sequencing data of intestinal contents indicated an increase in genus/species of Prevotella (Prevotella copri), Lactobacillus (Lactobacillus reuteri), Roseburia, Allobaculum, and Faecalibacterium prausnitzii, and decreased abundance of Helicobacter, Desulfovibrio, and Akkermansia (Akkermansia muciniphila) in synbiotic-treated rats compared to the MCAO surgery group. These findings confer the potential benefits of our novel synbiotic preparation for MCAO-induced neurological dysfunctions by reshaping the gut-brain-axis mediators in rats., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized primarily by cognitive impairment. Recent investigations have highlighted the potential of nutritional interventions that target the gut-brain axis, such as probiotics and prebiotics, in forestalling the onset of AD. In this study, whole-genome sequencing was employed to identify xylan as the optimal carbon source for the tryptophan metabolism regulating probiotic Clostridium sporogenes ( C. sporogenes ). Subsequent in vivo studies demonstrated that administration of a synbiotic formulation comprising C. sporogenes (1 × 10 10 CFU per day) and xylan (1%, w/w) over a duration of 30 days markedly enhanced cognitive performance and spatial memory faculties in the 5xFAD transgenic AD mouse model. The synbiotic treatment significantly reduced amyloid-β (Aβ) accumulation in the cortex and hippocampus of the brain. Importantly, synbiotic therapy substantially restored the synaptic ultrastructure in AD mice and suppressed neuroinflammatory responses. Moreover, the intervention escalated levels of the microbial metabolite indole-3-propionic acid (IPA) and augmented the relative prevalence of IPA-synthesizing bacteria, Lachnospira and Clostridium , while reducing the dominant bacteria in AD, such as Aquabacterium , Corynebacterium , and Romboutsia . Notably, synbiotic treatment also prevented the disruption of gut barrier integrity. Correlation analysis indicated a strong positive association between gut microbiota-generated IPA levels and behavioral changes. In conclusion, this study demonstrates that synbiotic supplementation significantly improves cognitive and intellectual deficits in 5xFAD mice, which could be partly attributed to enhanced IPA production by gut microbiota. These findings provide a theoretical basis for considering synbiotic therapy as a novel microbiota-targeted approach for the treatment of metabolic and neurodegenerative diseases.

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.

Depletion of beneficial microbes by modern lifestyle factors correlates with the rising prevalence of food allergies. Re-introduction of allergy-protective bacteria may be an effective treatment strategy. We characterized the fecal microbiota of healthy and food-allergic infants and found that the anaerobe Anaerostipes caccae (A. caccae) was representative of the protective capacity of the healthy microbiota. We isolated a strain of A. caccae from the feces of a healthy infant and identified lactulose as a prebiotic to optimize butyrate production by A. caccae in vitro. Administration of a synbiotic composed of our isolated A. caccae strain and lactulose increased luminal butyrate in gnotobiotic mice colonized with feces from an allergic infant and in antibiotic-treated specific pathogen-free (SPF) mice, and prevented or treated an anaphylactic response to allergen challenge. The synbiotic's efficacy in two models and microbial contexts suggests that it may be a promising approach for the treatment of food allergy., Competing Interests: Declaration of interests C.R.N. is a co-founder of ClostraBio, Inc., and portions of this work have been patented under US Patent Application US20210386796A1., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The use of synbiotics is emerging as a promising intervention strategy for regulating the gut microbiota and for preventing or reducing obesity, in comparison with the use of probiotics or prebiotics alone. A previous in vivo study revealed that Lacticaseibacillus paracasei K56 (L. paracasei K56) could alleviate obesity induced in high-fat-diet mice; however, the effect of the synbiotic combination of L. paracasei K56 and prebiotics in obese individuals has not been explored fully., Results: The effect of prebiotics on the proliferation of L. paracasei K56 was determined by spectrophotometry. The results showed that polydextrose (PG), xylooligosaccharide (XOS), and galactooligosaccharide (GOS) had a greater potential to be used as substrates for L. paracasei K56 than three other prebiotics (melitose, stachyose, and mannan-oligosaccharide). An in vitro fermentation model based on the feces of ten obese female volunteers was then established. The results revealed that K56&#95;GOS showed a significant increase in GOS degradation rate and short-chain fatty acid (SCFA) content, and a decrease in gas levels, compared with PG, XOS, GOS, K56&#95;PG, and K56&#95;XOS. Changes in these microbial biomarkers, including a significant increase in Bacteroidota, Bifidobacterium, Lactobacillus, Faecalibacterium, and Blautia and a decrease in the Firmicutes/Bacteroidota ratio and Escherichia-Shigella in the K56&#95;GOS group, were associated with increased SCFA content and decreased gas levels., Conclusion: This study demonstrates the effect of the synbiotic combination of L. paracasei K56 and GOS on obese individuals and indicates its potential therapeutic role in obesity treatment. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Insufficient dietary fiber intake can negatively affect the intestinal microbiome and, over time, may result in gut dysbiosis, thus potentially harming overall health. This randomized controlled trial aimed to improve the gut microbiome of individuals with low dietary fiber intake (<25 g/day) during a 7-week synbiotic intervention. The metabolically healthy male participants ( n = 117, 32 ± 10 y, BMI 25.66 ± 3.1 kg/m 2 ) were divided into two groups: one receiving a synbiotic supplement (Biotic Junior, MensSana AG, Forchtenberg, Germany) and the other a placebo, without altering their dietary habits or physical activity. These groups were further stratified by their dietary fiber intake into a low fiber group (LFG) and a high fiber group (HFG). Stool samples for microbiome analysis were collected before and after intervention. Statistical analysis was performed using linear mixed effects and partial least squares models. At baseline, the microbiomes of the LFG and HFG were partially separated. After seven weeks of intervention, the abundance of SCFA-producing microbes significantly increased in the LFG, which is known to improve gut health; however, this effect was less pronounced in the HFG. Beneficial effects on the gut microbiome in participants with low fiber intake may be achieved using synbiotics, demonstrating the importance of personalized synbiotics.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Probiotics and synbiotics have been intensively used in animal husbandry due to their advantageous roles in animals' health. However, there is a paucity of research on probiotic and synbiotic supplementation from maternal gestation to the postnatal growing phases of offspring piglets. Thus, we assessed the effects of dietary supplementation of these two additives to sows and offspring piglets on skeletal muscle and body metabolism, colonic microbiota composition, and metabolite profiles of offspring piglets. Pregnant Bama mini-pigs and their offspring piglets (after weaning) were fed either a basal diet or a basal diet supplemented with antibiotics, probiotics, or synbiotics. At 65, 95, and 125 days old, eight pigs per group were euthanized and sampled for analyses. Probiotics increased the intramuscular fat content in the psoas major muscle (PMM) at 95 days old, polyunsaturated fatty acid (PUFA) and n-3 PUFA levels in the longissimus dorsi muscle (LDM) at 65 days old, C16:1 level in the LDM at 125 days old, and upregulated ATGL , CPT-1 , and HSL expressions in the PMM at 65 days old. Synbiotics increased the plasma HDL-C level at 65 days old and TC level at 65 and 125 days old and upregulated the CPT-1 expression in the PMM at 125 days old. In addition, probiotics and synbiotics increased the plasma levels of HDL-C at 65 days old, CHE at 95 days old, and LDL-C at 125 days old, while decreasing the C18:1n9t level in the PMM at 65 days old and the plasma levels of GLU, LDH, and TG at 95 days old. Microbiome analysis showed that probiotic and synbiotic supplementation increased colonic Actinobacteria, Firmicutes, Verrucomicrobia, Faecalibacterium , Pseudobutyrivibrio , and Turicibacter abundances. However, antibiotic supplementation decreased colonic Actinobacteria, Bacteroidetes, Prevotella , and Unclassified&#95;Lachnospiraceae abundances. Furthermore, probiotic and synbiotic supplementation was associated with alterations in 8, 7, and 10 differential metabolites at three different age stages. Both microbiome and metabolome analyses showed that the differential metabolic pathways were associated with carbohydrate, amino acid, and lipid metabolism. However, antibiotic supplementation increased the C18:1n9t level in the PMM at 65 days old and xenobiotic biodegradation and metabolism at 125 days old. In conclusion, sow-offspring's diets supplemented with these two additives showed conducive effects on meat flavor, nutritional composition of skeletal muscles, and body metabolism, which may be associated with the reshaping of colonic microbiota and metabolites. However, antibiotic supplementation has negative effects on colonic microbiota composition and fatty acid composition in the PMM., Importance: The integral sow-offspring probiotic and synbiotic supplementation improves the meat flavor and the fatty acid composition of the LDM to some extent. Sow-offspring probiotic and synbiotic supplementation increases the colonic beneficial bacteria (including Firmicutes, Verrucomicrobia, Actinobacteria, Faecalibacterium , Turicibacter , and Pseudobutyrivibrio ) and alters the colonic metabolite profiles, such as guanidoacetic acid, beta-sitosterol, inosine, cellobiose, indole, and polyamine. Antibiotic supplementation in sow-offspring's diets decreases several beneficial bacteria (including Bacteroidetes, Actinobacteria, Unclassified&#95;Lachnospiraceae , and Prevotella ) and has a favorable effect on improving the fatty acid composition of the LDM to some extent, while presenting the opposite effect on the PMM., Competing Interests: The authors declare no conflict of interest.

A total of ninety-six weaned piglets were assigned to four dietary treatments in a 2 × 2 design. The treatments included: a standard milk formula (CTR); CTR + probiotics (6.4 × 10 8 cfu L -1 Bifidobacterium longum subsp. infantis CECT 7210 and 1.1 × 10 8 cfu L -1 Lactobacillus rhamnosus NH001) + prebiotics (galacto-oligosaccharides 4.36 g L -1 and human-milk-oligosaccharide 0.54 g L -1 ) (SYN); CTR + osteopontin (0.43 g L -1 ) (OPN); and CTR + SYN + OPN (CON). Daily records including feed intake, body weight, and clinical signs, were maintained throughout the 15-day trial. At the end of the study samples from blood, digestive content, and gut tissues were collected to determine serum TNF-α, intestinal fermentative activity (SCFA and ammonia), colonic microbiota (16S rRNA Illumina-MiSeq), histomorphology, and jejunal gene expression (Open-Array). No statistical differences were found in weight gain; however, the animals supplemented with osteopontin exhibited higher feed intake. In terms of clinical signs, synbiotic supplementation led to a shorter duration of diarrhoea episodes. Regarding gut health, the sequenced faecal microbiota revealed better control of potentially dysbiotic bacteria with the CON diet at day 15. In the colon compartment, a significant increase in SCFA concentration, a decrease in ammonia concentration, and a significant decrease in intraepithelial lymphocyte counts were particularly observed in CON animals. The supplemented diets were also associated with modified jejunal gene expression. The synbiotic combination was characterized by the upregulation of genes related to intestinal maturation (ALPI, SI) and nutrient transport (SLC13A1, SLC15A1, SLC5A1, SLC7A8), and the downregulation of genes related to the response to pathogens (GBP1, IDO, TLR4) or the inflammatory response (IDO, IL-1β, TGF-β1). Osteopontin promoted the upregulation of a digestive function gene (GCG). Correlational analysis between the microbiota population and various intestinal environmental factors (SCFA concentration, histology, and gene expression) proposes mechanisms of communication between the gut microbiota and the host. In summary, these results suggest an improvement in the colonic colonization process and a better modulation of the immune response when milk formula is supplemented with the tested synbiotic combined with osteopontin, benefiting from a synergistic effect.

Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as the optimal source of nutrition for infant growth and immune maturation, and its composition can be modulated by the maternal diet. In the present work, we investigated whether oral supplementation with Bifidobacterium breve M-16V and short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) to rat dams during gestation and lactation has an impact on the immune system and microbiota composition of the offspring at day 21 of life. On that day, blood, adipose tissue, small intestine (SI), mesenteric lymph nodes (MLN), salivary gland (SG), cecum, and spleen were collected. Synbiotic supplementation did not affect the overall body or organ growth of the pups. The gene expression of Tlr9 , Muc2 , IgA , and Blimp1 were upregulated in the SI, and the increase in IgA gene expression was further confirmed at the protein level in the gut wash. Synbiotic supplementation also positively impacted the microbiota composition in both the small and large intestines, resulting in higher proportions of Bifidobacterium genus, among others. In addition, there was an increase in butanoic, isobutanoic, and acetic acid concentrations in the cecum but a reduction in the small intestine. At the systemic level, synbiotic supplementation resulted in higher levels of immunoglobulin IgG2c in plasma, SG, and MLN, but it did not modify the main lymphocyte subsets in the spleen and MLN. Overall, synbiotic maternal supplementation is able to positively influence the immune system development and microbiota of the suckling offspring, particularly at the gastrointestinal level.

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., Competing Interests: Conflicts of interest “The authors declare no conflict of interest.”, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the microbiome from dysbiosis. The objective of this systematic review and meta-analysis was to assess the impact of MMAs on hemoglobin A1c (HbA1c) and biomarkers associated with (T1D). A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, National Knowledge Infrastructure, WeiPu, and WanFang Data up to 30 November 2023. Ten randomized controlled trials ( n = 630) were included, with study quality evaluated using the Cochrane risk-of-bias tool. Random-effect models with standardized mean differences (SMDs) were utilized. MMA supplementation was associated with improvements in HbA1c (SMD = -0.52, 95% CI [-0.83, -0.20]), daily insulin usage (SMD = -0.41, 95% confidence interval (CI) [-0.76, -0.07]), and fasting C-peptide (SMD = 0.99, 95% CI [0.17, 1.81]) but had no effects on FBG, CRP, TNF-α, IL-10, LDL, HDL, and the Shannon index. Subgroup analysis of HbA1c indicated that a long-term intervention (>3 months) might exert a more substantial effect. These findings suggest an association between MMAs and glycemic control in T1D. Further large-scale clinical trials are necessary to confirm these findings with investigations on inflammation and gut microbiota composition while adjusting confounding factors such as diet, physical activity, and the dose and form of MMA intervention.

The diversity and functionality of gut microbiota may play a crucial role in the function of human motor-related systems. In addition to traditional nutritional supplements, there is growing interest in microecologics due to their potential to enhance sports performance and facilitate post-exercise recovery by modulating the gut microecological environment. However, there is a lack of relevant reviews on this topic. This review provides a comprehensive overview of studies investigating the effects of various types of microecologics, such as probiotics, prebiotics, synbiotics, and postbiotics, on enhancing sports performance and facilitating post-exercise recovery by regulating energy metabolism, mitigating oxidative-stress-induced damage, modulating immune responses, and attenuating bone loss. Although further investigations are warranted to elucidate the underlying mechanisms through which microecologics exert their effects. In summary, this study aims to provide scientific evidence for the future development of microecologics in athletics.

Myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), and long COVID are complex, multisystemic and long-term disabling conditions characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and long COVID suggest that the use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis, may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation and neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and long COVID.

The efficacy of prebiotics and probiotics (synbiotics when combined) to improve symptoms associated with autism spectrum disorder (ASD) has shown considerable inter-study variation, likely due to the complex, heterogeneous nature of the disorder and its associated behavioral, developmental, and gastrointestinal symptoms. Here, we present a precision synbiotic supplementation study in 296 children and adults diagnosed with ASD versus 123 age-matched neurotypical controls. One hundred seventy ASD participants completed the study. Baseline and post-synbiotic assessment of ASD and gastrointestinal (GI) symptoms and deep metagenomic sequencing were performed. Within the ASD cohort, there were significant differences in microbes between subpopulations based on the social responsiveness scale (SRS2) survey ( Prevotella spp. , Bacteroides, Fusicatenibacter , and others) and gluten and dairy-free diets ( Bifidobacterium spp., Lactococcus, Streptococcus spp., and others). At the baseline, the ASD cohort maintained a lower taxonomic alpha diversity and significant differences in taxonomic composition, metabolic pathways, and gene families, with a greater proportion of potential pathogens, including Shigella, Klebsiella, and Clostridium, and lower proportions of beneficial microbes, including Faecalibacterium compared to controls. Following the 3-month synbiotic supplementation, the ASD cohort showed increased taxonomic alpha diversity, shifts in taxonomy and metabolic pathway potential, and improvements in some ASD-related symptoms, including a significant reduction in GI discomfort and overall improved language, comprehension, cognition, thinking, and speech. However, the open-label study design may include some placebo effects. In summary, we found that precision synbiotics modulated the gut microbiome and could be used as supplementation to improve gastrointestinal and ASD-related symptoms., Importance: Autism spectrum disorder (ASD) is prevalent in 1 out of 36 children in the United States and contributes to health, financial, and psychological burdens. Attempts to identify a gut microbiome signature of ASD have produced varied results. The limited pre-clinical and clinical population sizes have hampered the success of these trials. To understand the microbiome associated with ASD, we employed whole metagenomic shotgun sequencing to classify microbial composition and genetic functional potential. Despite being one of the most extensive ASD post-synbiotic assessment studies, the results highlight the complexity of performing such a case-control supplementation study in this population and the potential for a future therapeutic approach in ASD., Competing Interests: J.P., D.N., S.J., T.M., S.D., K.B., and S.T. are employed by Sun Genomics Inc. D.C.C. was co-supported by Sun Genomics Inc. J.A. and R.K.-B. are co-founders of Gut-Brain Axis Therapeutics Inc., which is developing microbiome-based treatments for autism and other disorders.

Context: Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome-targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear., Objectives: This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population., Data Source: A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD., Data Extraction: Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies., Data Analysis: A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], -10.21; 95% confidence interval [CI], -13.29, -7.14; P < 0.001), aspartate aminotransferase (AST; ES, -8.86; 95%CI, -11.39, -6.32; P < 0.001), and γ-glutamyltransferase (ES, -5.56; 95%CI, -7.92, -3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, -8.69; 95%CI, -11.01, -6.37; P < 0.001) and ALT (ES, -9.82; 95%CI, -11.59, -8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, -11.40; 95%CI, -13.91, -8.88; P < 0.001) and ALT (ES, -11.87; 95%CI, -13.80, -9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, -2.96; 95%CI, -8.12, 2.18, P = 0.259; and ES, -4.69; 95%CI, -13.53, 4.15, P = 0.299, respectively)., Conclusion: Gut microbiome-targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome-targeted therapies in the treatment of the NAFLD population., Systematic Review Registration: PROSPERO registration no. CRD42022346998., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action., Methods: A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed., Results: Gut microbial therapy significantly decreased HOMA-IR (ES: -0.41; 95%CI: -0.52, -0.31; P < 0.001) and FI (ES: -0.59; 95%CI: -0.77, -0.41; P < 0.001). However, no significant effect was observed on FBS (ES: -0.17; 95%CI: -0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics., Conclusion: Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS., (© 2024. The Author(s).)

Background: Aging has been associated with a progressive loss of skeletal muscle quality, quantity and strength, which may result in a condition known as sarcopenia, leading to a decline in physical performance, loss of independence and reduced quality of life. While the cause of impaired physical functioning observed in elderly populations appears to be multifactorial, recent evidence suggests that age-associated alterations in gut microbiota could be a contributing factor. The primary objective will be to assess the effects of a dietary synbiotic formulation on sarcopenia-related functional outcomes such as handgrip strength, gait speed and physical performance within older individuals living independently. The secondary objective will be to examine associations between changes in gut microbiota composition, functional performance and lean muscle mass., Methods: Seventy-four elderly (60-85 years) participants will be randomized in a double-blind, placebo-controlled fashion to either an intervention or control group. The intervention group (n = 37) will receive oral synbiotic formulation daily for 16 weeks. The control group (n = 37) will receive placebo. Assessments of physical performance (including Short Physical Performance Battery, handgrip strength and timed up-and-go tests) and muscle ultrasonography will be performed at 4 time points (baseline and weeks 8, 16 and 20). Likewise, body composition via bioelectric impedance analysis and blood and stool samples will be collected at each time point. Dual-energy X-ray absorptiometry will be performed at baseline and week 16. The primary outcomes will be between-group changes in physical performance from baseline to 16 weeks. Secondary outcomes include changes in body composition, muscle mass and architecture, fecal microbiota composition and diversity, and fecal and plasma metabolomics., Discussion: Gut-modulating supplements appear to be effective in modifying gut microbiota composition in healthy older adults. However, it is unclear whether these changes translate into functional and/or health improvements. In the present study, we will investigate the effects of a synbiotic formulation on measures of physical performance, strength and muscle health in healthy older populations., Trial Registration: This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000652774) in May 2022., (© 2024. The Author(s).)

We aimed to investigate the role of Synbiotic preparations on the interaction of gut microbiota with AD development. APP/PS1 mice were randomized into APP/PS1 and Synbiotics groups, and C57BL/6J mice were used as wild type (WT) control group. The mice in the Synbiotics group and the APP/PS1 group were given Synbiotics and xylo-oligosaccharides for 3 months, respectively. The mice in the WT group were given the same amount of normal saline. Cognitive function was measured. Positron emission computed tomography/magnetic resonance imaging (PET/MRI) was used to detect fasting blood glucose level. Immunohistochemical assay, ELISA, western blot and qRT-PCR were carried out to detect inflammatory factors. DNA extraction of fecal sample was performed to carry out sequencing. Bioinformatics analysis, metabolites sample preparation and Liquid Chromatograph Mass Spectrometer (LC/MS) analysis were also performed. Synbiotics treatment can significantly ameliorate learning and memory competence by inhibiting Aβ protein deposition. Different bacteria in the intestine were significantly improved and changes in gut microbiota can affect the intestinal metabolism to affect multiple potential pathways after Synbiotics treatment. Synbiotics treatment can activate peroxisome proliferator activated receptor (PPARs) signaling pathway and significantly reduce neuroinflammation in APP/PS1 mice brains. Synbiotics treatment can effectively reduce neuro-inflammatory response through the regulation of intestinal microflora to delay AD development.

Synbiotics modulate the gut microbiome and contribute to the prevention of liver diseases such as metabolic-dysfunction-associated fatty liver disease (MAFLD). This study aimed to evaluate the effect of a randomized, placebo-controlled, double-blinded seven-week intervention trial on the liver metabolism in 117 metabolically healthy male participants. Anthropometric data, blood parameters, and stool samples were analyzed using linear mixed models. After seven weeks of intervention, there was a significant reduction in alanine aminotransferase (ALT) in the synbiotic group compared to the placebo group (-14.92%, CI: -26.60--3.23%, p = 0.013). A stratified analysis according to body fat percentage revealed a significant decrease in ALT (-20.70%, CI: -40.88--0.53%, p = 0.045) in participants with an elevated body fat percentage. Further, a significant change in microbiome composition (1.16, CI: 0.06-2.25, p = 0.039) in this group was found, while the microbial composition remained stable upon intervention in the group with physiological body fat. The 7-week synbiotic intervention reduced ALT levels, especially in participants with an elevated body fat percentage, possibly due to modulation of the gut microbiome. Synbiotic intake may be helpful in delaying the progression of MAFLD and could be used in addition to the recommended lifestyle modification therapy.

Introduction: Metabolic Dysfunction-associated Liver Disease (MASLD) represents a spectrum of conditions from simple fat accumulation to non-alcoholic steatohepatitis. The possible role of the intestinal microbiome on MASLD development has been in focus. Our study aimed to examine the effects of synbiotics on the liver steatosis, inflammation, and stool microbiome., Methods: A double-blind, placebo-controlled study was conducted involving 84 MASLD patients, defined by an elastometric attenuation coefficient (ATT) greater than 0.63 dB/cm/MHz with an alanine aminotransferase level above 40 U/L for men and 35 U/L for women. The patients were divided into an intervention group treated with a synbiotic with 64x10 9 CFU of Lactobacillus and Bifidobacterium and 6.4g of inulin and a control group treated with a placebo., Results: Using synbiotics for 12 weeks significantly decreased liver steatosis (ΔATT -0.006±0.023 vs -0.016±0.021 dB/cm/MHz, p=0.046). The group of patients treated with synbiotics showed a significant decrease in the level of high-sensitive C-reactive protein (Δhs-CRP 0 vs -0.7 mg/L, p≤0.001). Synbiotics enriched the microbiome of patients in the intervention group with the genera Lactobacillus, Bifidobacterium, Faecalibacterium , and Streptococcus , by 81%, 55%, 51%, and 40%, respectively, with a reduction of Ruminococcus and Enterobacterium by 35% and 40%. Synbiotic treatment significantly shortened the gut transition time (ΔGTT -5h vs. -10h, p=0.031)., Conclusion: Synbiotics could be an effective and safe option that could have place in MASLD treatment., (© 2024 Miloš Mitrović et al., published by Sciendo.)

Background: Type 2 diabetes mellitus (T2DM) is considered a global health challenge with increasing prevalence in recent years. One of the key elements in managing T2DM patients is controlling their lipid profile. Recent studies suggest microbiome-targeted therapy (MTT) as a treatment strategy for enhancing lipid profiles in these patients., Objective: The current study aimed to investigate the impact of MTT on lipid indices of T2DM patients by performing an umbrella approach., Methods: Three international databases including PubMed, Scopus, and Web of Science were searched from inception up to April 2023 to find meta-analyses evaluating the impact of MTT (prebiotics, probiotics, and synbiotics) on the lipid profile of T2DM patients. Two independent researchers extracted data from the relevant meta-analyses. To find the source of heterogeneity various subgroup analyses were performed. Comprehensive Meta-Analyses (CMA) software version 3 was utilized for the final analysis., Results: Based on the results of the current study, MTT had on significant effects total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) (ES: - 0.092; 95%CI: -0.111, -0.074; P< 0.001, ES: -0.109; 95%CI: -0.137, -0.081; P< 0.001, ES: -0.036; 95%CI: -0.068, -0.005; P= 0.024, ES: 0.109; 95%CI: 0.056, 0.162; P<0.000, respectively). In subgroup analysis, probiotics showed the most substantial effect on all lipid biomarkers., Conclusion: This research has provided promising insights into the potential impact of MTT on lipid levels in patients diagnosed with T2DM. Notably, MTT had the greatest impact on HDL levels, followed by TG, TC, and LDL. As a result of our study, MTT is recommended as an adjunctive therapeutic option for T2DM treatment due to its capability to regulate lipid profiles., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Synbiotic is defined as the dietary mixture that comprises both probiotic microorganisms and prebiotic substrates. The concept has been steadily gaining attention owing to the rising recognition of probiotic, prebiotics, and gut health. Among prebiotic substances, oligosaccharides demonstrated considerable health beneficial effects in varieties of food products and their combination with probiotics have been subjected to full range of evaluations. This review delineated the landscape of studies using microbial cultures, cell lines, animal model, and human subjects to explore the functional properties and host impacts of these combinations. Overall, the results suggested that these combinations possess respective metabolic properties that could facilitate beneficial activities therefore could be employed as dietary interventions for human health improvement and therapeutic purposes. However, uncertainties, such as applicational practicalities, underutilized analytical tools, contradictory results in studies, unclear mechanisms, and legislation hurdles, still challenges the broad utilization of these combinations. Future studies to address these issues may not only advance current knowledge on probiotic-prebiotic-host interrelationship but also promote respective applications in food and nutrition.

Prebiotic and probiotic combinations may lead to a synbiotic effect, demonstrating superior health benefits over either component alone. Using the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME ® ) model, the effects of repeated supplementation with inulin (prebiotic, which is expected to provide a source of nutrition for the live microorganisms in the gut to potentially support optimal digestive health), Bacillus coagulans lactospore (probiotic), and a low and high dose of a synbiotic combination of the two on the gut microbial community activity and composition were evaluated. Test product supplementation increased the health-promoting short-chain fatty acids acetate and butyrate compared with levels recorded during the control period, demonstrating a stimulation of saccharolytic fermentation. This was likely the result of the increased abundance of several saccharolytic bacterial groups, including Megamonas , Bifidobacterium , and Faecalibacterium , following test product supplementation. The stimulation of acetate and butyrate production, as well as the increased abundance of saccharolytic bacterial groups were more evident in treatment week 3 compared with treatment week 1, demonstrating the value of repeated product administration. Further, the synbiotic formulations tended to result in greater changes compared with prebiotic or probiotic alone. Overall, the findings demonstrate a synbiotic potential for inulin and B. coagulans lactospore and support repeated administration of these products, indicating a potential for promoting gut health.

Background: A potential limelight is flashed on the Gut Microbiota (GM) in the human body, which confers additional psychological as well as physiological attributes to health. Other than just occupying a wide portion of the gastrointestinal tract, it also plays numerous functions in the systems of the body. Gut Microbiota is largely responsible for a considerably vast array of conditions such as obesity, diabetes ,other metabolic disorders, and cardiovascular disorders. Strategies targeting the gut microbiota have been proposed as a promising approach for the management of these disorders., Objective: This review aims to summarize the different strategies targeting the gut microbiota for the management of several disorders and to highlight the importance of a sustainable approach., Methods: A comprehensive literature search was conducted using various databases between 2008 and 2022 that focused on the use of prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, dietary interventions, and antibiotics., Results: Different strategies targeting the gut microbiota for the management of several disorders were identified, including probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and dietary interventions. Modification in diet and lifestyle, allowing favorable microbiota growth in the stomach, intake of prebiotics and probiotics, and fecal microbiota transplantation are amongst the widely accepted recent approaches allowing the application of GM in the field of treatment., Conclusion: Although considerable steps in enhancing and understanding the mechanism of treatment with the help of gut microbiota are under progress, much diversified and elaborate research must be conducted in order to enhance and implement the use of GM with high effectiveness., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Diabetes is a metabolic disorder whose prevalence has become a worrying condition in recent decades. Chronic diabetes can result in serious health conditions such as impaired kidney function, stroke, blindness, and myocardial infarction. Despite a variety of currently available treatments, cases of diabetes and its complications are on the rise. This review article provides a comprehensive account of the ameliorative effect of prebiotics and probiotics individually or in combination i.e. synbiotics on health complications induced by Type 2 Diabetes Mellitus (T2DM). Recent advances in the field underscore encouraging outcomes suggesting the consumption of synbiotics leads to favorable changes in the gut microbiota. These changes result in the production of bioactive metabolites such as short-chain fatty acids (crucial for lowering blood sugar levels), reducing inflammation, preventing insulin resistance, and encouraging the release of glucagon-like peptide-1 in the host. Notably, novel strategies supplementing synbiotics to support gut microbiota are gaining attraction as pivotal interventions in mitigating T2DM-induced health complications. Thus, by nurturing a symbiotic relationship between prebiotics and probiotics i.e. synbiotics, these interventions hold promise in reshaping the microbial landscape of the gut thereby offering a multifaceted approach to managing T2DM and its associated morbidities. Supporting the potential of synbiotics underscores a paradigm shift toward holistic and targeted interventions in diabetes management, offering prospects for improved outcomes and enhanced quality of life for affected individuals. Nevertheless, more research needs to be done to better understand the single and multispecies pre/pro and synbiotics in the prevention and management of T2DM-induced health complications.

Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

The role of gut microbiome in health, a century-old concept, has been on the center stage of medical research recently. While different body sites, disease conditions, and populations have been targeted, neonatal and early infancy appear to be the most suitable period for such interventions. It is intriguing to note that, unlike traditional use in diarrhea and maintenance of gastrointestinal health, microbiome-mediating therapies have now addressed the most serious medical conditions in young infants such as necrotizing enterocolitis and neonatal sepsis. Unfortunately, almost all new endeavors in this space have been carried out in the Western world leaving behind millions of neonates that can benefit from such manipulations while serving as a large resource for further learning. In this review, an attempt has been made to quantify the global burden of neonatal morbidity and mortality, examples presented on interventions that have failed as a result of drawing from studies conducted in the West, and a case made for manipulating the neonatal gut microbiome to address the biggest killers in early life. A brief comparative analysis has been made to demonstrate the differences in the gut microbiota of North and South and a large clinical trial of synbiotics conducted by our group in a South Asian setting has been presented. Although challenging, the value of conducting such global health research is introduced with an intent to invite medical scientists to engage in well-planned, scientifically robust research endeavors. This can bring about innovation while saving and serving the most vulnerable citizens now and protecting them from the negative health consequences in the later part of their lives, ultimately shaping a resilient and equitable world as pledged by 193 United Nations member countries in 2015.

Food allergy has caused lots of global public health issues, particularly in developed countries. Presently, gut microbiota has been widely studied on allergy, while the role of dysbiosis in food allergy remains unknown. Scientists found that changes in gut microbial compositions and functions are strongly associated with a dramatic increase in the prevalence of food allergy. Altering microbial composition is crucial in modulating food antigens' immunogenicity. Thus, the potential roles of probiotics, prebiotics, synbiotics, and postbiotics in affecting gut bacteria communities and the immune system, as innovative strategies against food allergy, begins to attract high attention of scientists. This review briefly summarized the mechanisms of food allergy and discussed the role of the gut microbiota and the use of probiotics, prebiotics, synbiotics, and postbiotics as novel therapies for the prevention and treatment of food allergy. The perspective studies on the development of novel immunotherapy in food allergy were also described. A better understanding of these mechanisms will facilitate the development of preventive and therapeutic strategies for food allergy.

Synbiotics combine the concepts of probiotics and prebiotics to synergistically enhance the health-associated effects of both components. Previously, we have shown that the intestinal persistence of inulin-utilizing L. plantarum Lp900 is significantly increased in rats fed an inulin-supplemented, high-calcium diet. Here we employed a competitive population dynamics approach to demonstrate that inulin and GOS can selectively enrich L. plantarum strains that utilize these substrates for growth during in vitro cultivation, but that such enrichment did not occur during intestinal transit in rats fed a GOS or inulin-supplemented diet. The intestinal persistence of all L. plantarum strains increased irrespective of their prebiotic utilization phenotype, which was dependent on the calcium level of the diet. Analysis of fecal microbiota and intestinal persistence decline rates indicated that prebiotic utilization capacity did not selectively stimulate intestinal persistence in prebiotic supplemented diets. Moreover, microbiota and organic acid profile analyses indicate that the prebiotic utilizing probiotic strains are vastly outcompeted by the endogenous prebiotic-utilizing microbiota, and that the collective enhanced persistence of all L. plantarum strains is most likely explained by their well-established tolerance to organic acids.

The gut microbiota is a key factor in the correct development of the gastrointestinal immune system. Studies have found differences between the gut microbiota of newborns delivered by cesarean section compared to those vaginally delivered. Our objective was to evaluate the effect of ingestion of probiotics, prebiotics, or synbiotics during pregnancy and/or lactation on the development of the gut microbiota of the C-section newborns. We selected experimental studies in online databases from their inception to October 2021. Of the 83 records screened, 12 met the inclusion criteria. The probiotics used belonged to the genera Lactobacillus , Bifidobacterium , Propionibacterium , and Streptococcus , or a combination of those, with dosages varying between 2 × 10 6 and 9 × 10 11 CFU per day, and were consumed during pregnancy and/or lactation. Probiotic strains were combined with galacto-oligosaccharides, fructo-oligosaccharides, or bovine milk-derived oligosaccharides in the synbiotic formulas. Probiotic, prebiotic, and synbiotic interventions led to beneficial gut microbiota in cesarean-delivered newborns, closer to that in vaginally delivered newborns, especially regarding Bifidobacterium colonization. This effect was more evident in breastfed infants. The studies indicate that this beneficial effect is achieved when the interventions begin soon after birth, especially the restoration of bifidobacterial population. Changes in the infant microbial ecosystem due to the interventions seem to continue after the end of the intervention in most of the studies. More interventional studies are needed to elucidate the optimal synbiotic combinations and the most effective strains and doses for achieving the optimal gut microbiota colonization of C-section newborns.

The effects of synbiotic yogurt supplemented with inulin on the pathological manifestations and gut microbiota-bile acid axis were investigated using a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) mice model. Female C57BL/6J mice were injected subcutaneously with DHEA at a dose of 6 mg/100 g BW for 20 days to establish a PCOS mouse model. Then, the PCOS mice were treated with yogurt containing inulin (6% w / w ) at 15 mL/kg BW for 24 days. Results showed that supplementation of synbiotic yogurt enriched with inulin to PCOS mice decreased the body weight gain, improved estrus cycles and ovary morphology, and reduced the levels of luteinizing hormone while increasing the levels of follicle-stimulating hormone and interleukin-22 in serum. At the genus level, synbiotic yogurt increased the relative abundance of Lactobacillus , Bifidobacterium, and Akkermansia . PICRUSt analysis indicated that KEGG pathways including bile acid biosynthesis were changed after inulin-enriched synbiotic yogurt supplementation. Synbiotic yogurt enriched with inulin also modulated the bile acid profiles. In conclusion, inulin-enriched synbiotic yogurt alleviated reproductive dysfunction and modulated gut microbiota and bile acid profiles in PCOS mice.