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The gut microbiota is a changing ecosystem, containing trillions of bacteria, continuously shaped by many factors, such as dietary habits, seasonality, lifestyle, stress, antibiotics use, or diseases. A healthy host–microorganisms balance must be respected in order to optimally maintain the intestinal barrier and immune system functions and, consequently, prevent disease development. In the past several decades, the adoption of modern dietary habits has become a growing health concern, as it is strongly associated with obesity and related metabolic diseases, promoting inflammation and both structural and behavioral changes in gut microbiota. In this context, novel dietary strategies are emerging to prevent diseases and maintain health. However, the consequences of these different diets on gut microbiota modulation are still largely unknown, and could potentially lead to alterations of gut microbiota, intestinal barrier, and the immune system. The present review aimed to focus on the impact of single food components (macronutrients and micronutrients), salt, food additives, and different dietary habits (i.e., vegan and vegetarian, gluten-free, ketogenic, high sugar, low FODMAP, Western-type, and Mediterranean diets) on gut microbiota composition in order to define the optimal diet for a healthy modulation of gut microbiota.

This review delves into the increasing interest in probiotics and paraprobiotics as a viable alternative to antibiotics in aquaculture, highlighting their potential to enhance fish health and prevent diseases. As the aquaculture industry continues its global expansion, addressing the challenges associated with disease outbreaks in high-density fish populations becomes imperative. The review underscores the promising role of probiotics and paraprobiotics as a sustainable strategy to mitigate these challenges. The diverse positive impacts of various probiotic strains such as Arthrobacter , Bacillus , Lactobacillus , Bifidobacterium , Clostridium , and others emphasize their roles in enhancing growth, resistance to diseases (including bacterial, viral, and parasitic infections), stress reduction, water quality management, and environmental sustainability. Challenges such as stability, host specificity, and regulatory considerations must be addressed to optimize the use of probiotics in aquaculture. Additionally, paraprobiotics, or non-viable microbial cells, present a safer alternative to the criticized antibiotics and even live probiotics in environments where microbial viability poses a risk. These inactivated cells retain the ability to modulate the immune system and improve gut health, offering a promising complementary approach to fish disease prevention. The review advocates for a systematic approach combining research, innovation, and collaboration to effectively integrate probiotics and paraprobiotics into fish farming practices. Furthermore, the mechanisms by which probiotics and paraprobiotics modulate gut microbiota, produce antimicrobial compounds, and strengthen fish’s immune system have been elucidated. Moreover, the practical applications of probiotics in fish farming, including optimal administration methods and the challenges and limitations faced by the industry, have been discussed. Emphasis on the importance of continued research to explore new probiotic and paraprobiotic strains and develop innovative delivery systems to ensure the sustainability of aquaculture has been discussed. By enhancing fish health, reducing the need for antibiotics, and improving water quality, probiotics, and paraprobiotics contribute to more sustainable and environmentally responsible aquaculture operations.

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.

Despite the approval of several artificial nanotherapeutics for the treatment of triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and the high cost of large-scale production, still restrict their long-term application. In contrast, plant-derived extracellular vesicles (PEVs) exhibit promising potential in cancer therapy due to their negligible systemic toxicity, high bioavailability and cost- effectiveness. In this study, we developed an alternative strategy to inhibit TNBC via Platycodon grandiflorum (PG)-derived extracellular vesicles (PGEVs). The PGEVs were isolated by ultracentrifugation and sucrose gradient centrifugation method and contained adequate functional components such as proteins, lipids, RNAs and active molecules. PGEVs exhibited remarkable stability, tolerating acidic digestion and undergoing minimal changes in simulated gastrointestinal fluid. They were efficiently taken up by tumor cells and induced increased production of reactive oxygen species (ROS), leading to tumor cell proliferation inhibition and apoptosis, particularly in the TNBC cell line 4T1. Additionally, PGEVs facilitated the polarization of tumor-associated macrophages (TAMs) toward M1 phenotype and increased the secretion of pro-inflammatory cytokines. Further in vivo investigations revealed that PGEVs efficiently accumulated in 4T1 tumors and exerted significant therapeutic effects through boosting systemic anti-tumor immune responses and modulating the gut microbiota whether administered orally or intravenously (i.v.). In conclusion, these findings highlight PGEVs as a promising natural, biocompatible and efficient nanotherapeutic candidate for treating TNBC. Graphical Abstract

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.

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. A novel enzyme-like biomimetic oral-agent ZnPBA@YCW could successfully regulate gut flora by significantly downgrading Escherichia coli's occupied ecological niche, enhancing the bacterial biodiversity while increasing the abundance of probiotics with anti-inflammatory phenotype. Moreover, it breaks the vicious cycle of ROS-inflammation, making it a highly efficient treatment option for treating inflammatory bowel disease. [Display omitted] •A novel enzyme-like oral-agent ZnPBA@YCW has been developed for the first time, using YCW as the outer shell and ZnPBA nanozyme inside.•ZnPBA@YCW is able to adhere to E. coli and subsequently releases ZnPBA nanozyme for removal of E. coli.•ZnPBA@YCW exhibits remarkable capability in restoring redox homeostasis.•ZnPBA@YCW can effectively regulate gut microbiome.

Traditional herbal medicine (THM) is used worldwide for its safety and effectiveness against various diseases. Huoxiang Zhengqi (HXZQ) is an extensively used Chinese THM formula targeting gastrointestinal disordered gastroenteritis via regulating the intestinal microbiome/immuno-microenvironment. However, the specific mechanisms remain largely unexplored, besides as a lifestyle drug, its safety on the gut microbiome homeostasis has never been investigated. In this study, the effects of HXZQ on the gut microbiome of healthy adults were investigated for the first time, and the antibiotic-induced gut microbiota dysbiosis mice model was applied for verification. Based on healthy adults, our results revealed that HXZQ exhibited mild and positive impacts on the bacterial diversity and the composition of the gut microbiome in a healthy state. As for an unhealthy state of the gut microbiome (with low bacterial diversity and deficient compositions), HXZQ significantly restored the bacterial diversity and recovered the abundance of Bacteroidetes . In the antibiotic-induced mice model, HXZQ distinctly revived the deficient gut microbial compositions impaired by antibiotics. At the genus level, the abundances that responded most strongly and positively to HXZQ were Bifidobacterium in healthy adults and Muribaculaceae , Lactobacillus , and Akkermansia in mice. In contrast, the abundance of Blautia in healthy adults, Enterococcus , and Klebsiella in mice showed inversely associated with HXZQ administration. At last, HXZQ might exhibit an anti-inflammatory effect by regulating the concentration of interleukin-6 in plasma while causing no significant changes in the colon tissue structure in mice. In conclusion, our results elucidate that the safety of HXZQ in daily use further reveals the modulatory effects of HXZQ on gut microbial community structure. These results will provide new insights into the interaction of THM and gut microbiome homeostasis and clues about the safe use of THM as a lifestyle drug for its further development.

Undernutrition is associated with gut microbiota unbalance, and probiotics are believed to restore it and improve gut integrity. A randomized double-blind controlled trial was conducted to evaluate the efficacy of gummy L. plantarum Dad-13 (108−9 CFU/3 g) to prevent the progression of severe undernutrition. Two groups of moderate undernutrition infants were involved in this study, namely the placebo (n = 15) and probiotics (n = 15) groups, and were required to consume the product for 50 days. 16S rRNA sequencing and qPCR were used for gut microbiota analysis, and gas chromatography was used to analyze Short-Chain Fatty Acid (SCFA). The daily food intake of both groups was recorded using food records. Our results revealed that the probiotic group had better improvements regarding the anthropometry and nutritional status. In addition, L. plantarum Dad-13 modulated the butyric acid-producing bacteria to increase and inhibit the growth of Enterobacteriaceae. This gut modulation was associated with the increment in SCFA, especially total SCFA, propionic, and butyric acid. The number of L. plantarum was increased after the probiotic intervention. However, L. plantarum Dad-13 was not able to change the alpha and beta diversity. Therefore, L. plantarum Dad-13 has been proven to promote the growth of beneficial bacteria.

Dairy products—encompassing yogurt, kefir, cheese, and cultured milk beverages—are emerging as versatile, food-based modulators of gut microbiota and host physiology. This review synthesizes mechanistic insights demonstrating how live starter cultures and their fermentation-derived metabolites (short-chain fatty acids, bioactive peptides, and exopolysaccharides) act synergistically to enhance microbial diversity, reinforce epithelial barrier integrity via upregulation of tight-junction proteins, and modulate immune signaling. Clinical evidence supports significant improvements in metabolic parameters (fasting glucose, lipid profiles, blood pressure) and reductions in systemic inflammation across metabolic syndrome, hypertension, and IBS cohorts. We highlight critical modulatory factors—including strain specificity, host enterotypes and FUT2 genotype, fermentation parameters, and matrix composition—that govern probiotic engraftment, postbiotic yield, and therapeutic efficacy. Despite promising short-term outcomes, current studies are limited by heterogeneous designs and brief intervention periods, underscoring the need for long-term, adaptive trials and integrative multi-omics to establish durability and causality. Looking forward, precision nutrition frameworks that harness baseline microbiota profiling, host genetics, and data-driven fermentation design will enable bespoke fermented dairy formulations, transforming these traditional foods into next-generation functional matrices for targeted prevention and management of metabolic, inflammatory, and neuroimmune disorders.

The gut microbiota is composed of bacteria, archaea, phages, and protozoa. It is now well known that their mutual interactions and metabolism influence host organism pathophysiology. Over the years, there has been growing interest in the composition of the gut microbiota and intervention strategies in order to modulate it. Characterizing the gut microbial populations represents the first step to clarifying the impact on the health/illness equilibrium, and then developing potential tools suited for each clinical disorder. In this review, we discuss the current gut microbiota manipulation strategies available and their clinical applications in personalized medicine. Among them, FMT represents the most widely explored therapeutic tools as recent guidelines and standardization protocols, not only for intestinal disorders. On the other hand, the use of prebiotics and probiotics has evidence of encouraging findings on their safety, patient compliance, and inter-individual effectiveness. In recent years, avant-garde approaches have emerged, including engineered bacterial strains, phage therapy, and genome editing (CRISPR-Cas9), which require further investigation through clinical trials.