Ageing is characterised by a progressive increase in systemic inflammation and especially neuroinflammation. Neuroinflammation is associated with altered brain states that affect behaviour, such as an increased level of anxiety with a concomitant decline in cognitive abilities. Although multiple factors play a role in the development of neuroinflammation, microglia have emerged as a crucial target. Microglia are the only macrophage population in the CNS parenchyma that plays a crucial role in maintaining homeostasis and in the immune response, which depends on the activation and subsequent deactivation of microglia. Therefore, microglial dysfunction has a major impact on neuroinflammation. The gut microbiota has been shown to significantly influence microglia from birth to adulthood in terms of development, proliferation, and function. Diet is a key modulating factor that influences the composition of the gut microbiota, along with prebiotics that support the growth of beneficial gut bacteria. Although the role of diet in neuroinflammation and behaviour has been well established, its relationship with microglia functionality is less explored. This article establishes a link between diet, animal behaviour and the functionality of microglia. The results of this research stem from experiments on mouse behaviour, i.e., memory, anxiety, and studies on microglia functionality, i.e., cytochemistry (phagocytosis, cellular senescence, and ROS assays), gene expression and protein quantification. In addition, shotgun sequencing was performed to identify specific bacterial families that may play a crucial role in the brain function. The results showed negative effects of long-term consumption of a high fat diet on ageing mice, epitomised by increased body weight, glucose intolerance, anxiety, cognitive impairment and microglia dysfunction compared to ageing mice on a control diet. These effects were a consequence of the changes in gut microbiota modulated by the diet. However, by adding the prebiotics fructo- and galacto-oligosaccharides, we were able to mitigate the deleterious effects of a long-term high-fat diet.

The beneficial effects of probiotics for the improvement of metabolic disorders have been studied intensively; however, these effects are evident in a probiotic strain-specific and disease-specific manner. Thus, it is still essential to evaluate the efficacy of each strain against a target disease. Here, we present an anti-obese and anti-diabetic probiotic strain, Lactiplantibacillus plantarum APsulloc331261 (GTB1™), which was isolated from green tea and tested for safety previously. In high-fat-diet-induced obese mice, GTB1™ exerted multiple beneficial effects, including significant reductions in adiposity, glucose intolerance, and dyslipidemia, which were further supported by improvements in levels of circulating hormones and adipokines. Lipid metabolism in adipose tissues was restored through the activation of PPAR/PGC1α signaling by GTB1™ treatment, which was facilitated by intestinal microbiota composition changes and short-chain fatty acid production. Our findings provide evidence to suggest that GTB1™ is a potential candidate for probiotic supplementation for comprehensive improvement in metabolic disorders.

BACKGROUND: Targeting gut dysbiosis to treat chronic diseases or to alleviate the symptoms is a new direction for medical adjuvant therapies. Recently, postbiotics have received considerable attention as they are non-viable probiotic preparations that confer various health benefits to the host without the safety problems associated with using live microbial cells.
OBJECTIVE: The aim of the study is to obtain selenium (Se) and zinc (Zn) enriched Saccharomyces boulardii postbiotic biomass and to analyze its modulation effect because these minerals play an important role in reducing gut dysbiosis linked to cardiovascular (CV) diseases.
METHODS: The effect of the S. boulardii and Se/Zn enriched yeast postbiotics on CV microbial fingerprint was studied in vitro using the gastrointestinal system (GIS 1) and analyzed by microbiological, chemical, and qPCR methods.
RESULTS: There was a 2.2 log CFU/mL increase in the total bacterial load after SeZn postbiotic treatment and in the qPCR counts of Firmicutes phyla for both treatments. Beneficial taxa, Bifidobacterium spp. and Lactobacillus spp., as well as Bacteroides spp. were up to 1.5 log higher after mineral- enriched postbiotic application, while the acetic acid level increased.
CONCLUSIONS: These preliminary studies highlight the therapeutic potential of using Se/Zn enriched yeast postbiotics as adjuvants for clinical treatments of CV diseases.

Vine-growing for the production of wine is one of the oldest and most important agricultural activities worldwide, but the winemaking process leads to vast amounts of waste. Viticulture and vinification by-products have many bioactive molecules, including polyphenols, prebiotic fibers, organic acids, and minerals. While research on the specific human health effects of grapevine residues (pomace, seeds, barks, stalks, canes, and leaves) is still ongoing, the available data suggest the potential to positively modulate the normal and dysbiotic gut microbiota (GM) using polyphenol-rich extracts obtained from winery by-products. This review provides an updated summary of the in vitro and in vivo evidence in animal models and humans concerning the ability of polyphenol-rich winery residue to be used as a GM modulator that supports their nutraceutical applications as a functional ingredient. Additionally, this review aims to enhance interest in viticulture waste (grapevine stems and leaves), as the levels of polyphenols are similar to those found in red grapes or seeds. However, more research is still needed to obtain innovative products. The valorization of winery residues is not only environmentally friendly; it can also be economically beneficial, creating added-value nutraceuticals that modulate microbiota and a new revenue stream for wine producers.

Mushroom polysaccharides are recognized as \"biological response modifiers\". Besides several bioactivities, a growing interest in their prebiotic potential has been raised due to the gut microbiota modulation potential. This review comprehensively summarizes mushroom polysaccharides\' biological properties, structure-function relationship, and underlying mechanisms. It provides a recent overview of the key findings in the field (2018-2024). Key findings and limitations on structure-function correlation are discussed. Although most studies focus on β-glucans or extracts, α-glucans and chitin have gained interest. Prebiotic capacity has been associated with α-glucans and chitin, while antimicrobial and wound healing potential is attributed to chitin. However, further research is of utmost importance. Human fecal fermentation is the most reported approach to assess prebiotic potential, indicating impacts on intestinal biological, mechanical, chemical and immunological barriers. Gut microbiota dysbiosis has been directly connected with intestinal, cardiovascular, metabolic, and neurological diseases. Concerning gut microbiota modulation, animal experiments have suggested proinflammatory cytokines reduction and redox balance re-establishment. Most literature focused on the anticancer and immunomodulatory potential. However, anti-inflammatory, antimicrobial, antiviral, antidiabetic, hypocholesterolemic, antilipidemic, antioxidant, and neuroprotective properties are discussed. A significant overview of the gaps and research directions in synergistic effects, underlying mechanisms, structure-function correlation, clinical trials and scientific data is also given.

Reactive oxygen species (ROS), immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease (IBD). Herein, a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed, using yeast cell wall (YCW) as the outer shell and zinc-doped Prussian blue analogue (ZnPBA) nanozyme inside. When orally administered, the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E. coli, meanwhile exhibiting improved intestinal epithelial barrier repair. Moreover, it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway. More importantly, the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity, significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E. coli to the same level as normal mice. Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.

Our investigation intended to analyze the effects of sulfated polysaccharides from Caulerpa racemosa (SPCr) in attenuating obesity-induced cardiometabolic syndrome via regulating the protein arginine N-methyltransferase 1-asymmetric dimethylarginine-dimethylarginine dimethylamino-hydrolase (PRMT1-DDAH-ADMA) with the mammalian target of rapamycin-Sirtuin 1-5\' AMP-activated protein kinase (mTOR-SIRT1-AMPK) pathways and gut microbiota modulation. This is a follow-up study that used SPs from previous in vitro studies, consisting of 2,3-di-O-methyl-1,4,5-tri-O-acetylarabinitol, 2,3,4,6-tetra-O-methyl-D-mannopyranose, and type B ulvanobiuronicacid 3-sulfate. A total of forty rats were randomly divided into four treatment groups: Group A received a standard diet; Group B was provided with a diet enriched in cholesterol and fat (CFED); and Groups C and D were given the CFED along with ad libitum water, and daily oral supplementation of 65 or 130 mg/kg of body weight (BW) of SPCr, respectively. Group D showed the lowest low-density lipoprotein, triglyceride, total cholesterol, and blood glucose levels, and the highest HDL level compared to the other groups in this study. These results in the group fed high-dose SPCr demonstrated a significant effect compared to the group fed low-dose SPCr (p < 0.0001), as well as in total cholesterol and blood glucose (p < 0.05). Supplementation with SPCr was also observed to have an upregulation effect on peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha, interleukin 10, Sirtuin 1, DDAH-II, superoxide dismutase (SOD) cardio, and AMPK, which was also followed by a downregulation of PRMT-1, TNF-α, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, and mTOR. Interestingly, gut microbiota modulation was also observed; feeding the rats with a cholesterol-enriched diet shifted the gut microbiota composition toward the Firmicutes level, lowered the Bacteroidetes level, and increased the Firmicutes level. A dose of 130 mg/kg BW of SPCr is the recommended dose, and investigation still needs to be continued in clinical trials with humans to see its efficacy at an advanced level.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage damage and synovial inflammation and carries an enormous public health and economic burden. It is crucial to uncover the potential mechanisms of OA pathogenesis to develop new targets for OA treatment. In recent years, the pathogenic role of the gut microbiota in OA has been well recognized. Gut microbiota dysbiosis can break host-gut microbe equilibrium, trigger host immune responses and activate the \"gut-joint axis\", which aggravates OA. However, although the role of the gut microbiota in OA is well known, the mechanisms modulating the interactions between the gut microbiota and host immunity remain unclear. This review summarizes research on the gut microbiota and the involved immune cells in OA and interprets the potential mechanisms for the interactions between the gut microbiota and host immune responses from four aspects: gut barrier, innate immunity, adaptive immunity and gut microbiota modulation. Future research should focus on the specific pathogen or the specific changes in the gut microbiota composition to identify the related signaling pathways involved in the pathogenesis of OA. In addition, future studies should include more novel interventions on immune cell modifications and gene regulation of specific gut microbiota related to OA to validate the application of gut microbiota modulation in the onset of OA.

Pancreatic cancer (PC) has an unfavorable prognosis with few effective therapeutic options. This has led researchers to investigate the possible links between microbiota and PC. A disrupted gut microbiome can lead to chronic inflammation, which is involved in the pathogenesis of PC. In addition, some bacterial strains can produce carcinogens that promote the growth of cancer cells. Research has also focused on pancreatic and oral microbiota. Changes in these microbiota can contribute to the development and progression of PC. Furthermore, patients with periodontal disease have an increased risk of developing PC. The potential use of microbiota as a prognostic marker or to predict patients\' responses to chemotherapy or immunotherapy is also being explored. Overall, the role of microbiota-including the gut, pancreatic, and oral microbiota-in PC is an active research area. Understanding these associations could lead to new diagnostic and therapeutic targets for this deadly disease.

Heart failure (HF) is a global pandemic with increasing prevalence and mortality rates annually. Its main cause is myocardial infarction (MI), followed by rapid cardiac remodeling. Several clinical studies have shown that probiotics can improve the quality of life and reduce cardiovascular risk factors. This systematic review and meta-analysis aimed to investigate the effectiveness of probiotics in preventing HF caused by a MI according to a prospectively registered protocol (PROSPERO: CRD42023388870). Four independent evaluators independently extracted the data using predefined extraction forms and evaluated the eligibility and accuracy of the studies. A total of six studies consisting of 366 participants were included in the systematic review. Probiotics are not significant in intervening left ventricular ejection fraction (LVEF) and high-sensitivity C-reactive protein (hs-CRP) when compared between the intervention group and the control group due to inadequate studies supporting its efficacy. Among sarcopenia indexes, hand grip strength (HGS) showed robust correlations with the Wnt biomarkers (p < 0.05), improved short physical performance battery (SPPB) scores were also strongly correlated with Dickkopf-related protein (Dkk)-3, followed by Dkk-1, and sterol regulatory element-binding protein 1 (SREBP-1) (p < 0.05). The probiotic group showed improvement in total cholesterol (p = 0.01) and uric acid (p = 0.014) compared to the baseline. Finally, probiotic supplements may be an anti-inflammatory, antioxidant, metabolic, and intestinal microbiota modulator in cardiac remodeling conditions. Probiotics have great potential to attenuate cardiac remodeling in HF or post-MI patients while also enhancing the Wnt signaling pathway which can improve sarcopenia under such conditions.