SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.

Fish intestinal health under intensive aquaculture mode plays an important role in growth, development, and immune function. The present study was aimed to systematically investigate the differences of intestinal health between wild and cultured Monopterus albus by biochemical parameters, histomorphology, and molecular biology. A total of 15 healthy M. albus per group, with an average body weight of 45 g, were sampled to analyze intestinal health parameters. Compared with wild fish, the cultured M. albus in the foregut had lower trypsin, lipase, SOD, CAT, T-AOC, and GSH-Px activities (P < 0.05) and higher amylase activity and MDA content (P < 0.05). The villus circumference and goblet cells in the cultured group were significantly lower than those in the wild group (P < 0.05). In addition, the cultured fish showed lower relative expression levels of occludin, zo-1, zo-2, claudin-12, claudin-15, mucin5, mucin15, lysozyme, complement 3, il-10, tgf-β1, tgf-β2, and tgf-β3 (P < 0.05) and higher il-1β, il-6, il-8, tnf-a, and ifnγ mRNA expressions than those of wild fish (P < 0.05). In terms of gut microbiota, the cultured group at the phylum level displayed higher percentages of Chlamydiae and Spirochaetes and lower percentages of Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria, and Verrucomicrobia compared to the wild group (P < 0.05). At the genus level, higher abundances of Pseudomonadaceae_Pseudomonas and Spironema and lower abundances of Lactococcus and Cetobacterium were observed in the cultured group than in the wild group (P < 0.05). To our knowledge, this is the first investigation of the intestinal health status between wild and cultured M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, the present study showed significant differences in intestinal health between wild and cultured M. albus and the main manifestations that wild M. albus had higher intestinal digestion, antioxidant capacity, and intestinal barrier functions than cultured M. albus. These results would provide theoretical basis for the subsequent upgrading of healthy aquaculture technology and nutrient regulation of intestinal health of cultured M. albus.

The role of probiotics in regulating intestinal flora to enhance host immunity has recently received widespread attention. Altering the human gut microbiota may increase the predisposition to several disease phenotypes such as gut inflammation and metabolic disorders. The intestinal microbiota converts dietary nutrients into metabolites that serve as biologically active molecules in modulating regulatory functions in the host. Probiotics, which are active microorganisms, play a versatile role in restoring the composition of the gut microbiota, helping to improve host immunity and prevent intestinal disease phenotypes. This comprehensive review provides firsthand information on the gut microbiota and their influence on human health, the dietary effects of diet on the gut microbiota, and how probiotics alter the composition and function of the human gut microbiota, along with their corresponding effects on host immunity in building a healthy intestine. We also discuss the implications of probiotics in some of the most important human diseases. In summary, probiotics play a significant role in regulating the gut microbiota, boosting overall immunity, increasing the abundance of beneficial bacteria, and helping ameliorate the symptoms of multiple diseases.

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

Pullorum disease (PD) is a bacterial infection caused by Salmonella pullorum (S. pullorum) that affects poultry. It is highly infectious and often fatal. Antibiotics are currently the mainstay of prophylactic and therapeutic treatments for PD, but their use can lead to the development of resistance in pathogenic bacteria and disruption of the host\'s intestinal flora. We added neomycin sulfate and different doses of tannic acid (TA) to the drinking water of chicks at 3 days of age and infected them with PD by intraperitoneal injection of S. pullorum at 9 days of age. We analyzed intestinal histopathological changes and the expression of immune-related genes and proteins by using the plate smear method, histological staining, real-time fluorescence quantitative PCR, ELISA kits, and 16S rRNA Analysis of intestinal flora. The results demonstrate that S. pullorum induces alterations in the immune status and impairs the functionality of the liver and intestinal barrier. We found that tannic acid significantly ameliorated S. pullorum-induced liver and intestinal damage, protected the intestinal physical and chemical barriers, restored the intestinal immune barrier function, and regulated the intestinal flora. Our results showed that TA has good anti-diarrhoeal, growth-promoting, immune-regulating, intestinal barrier-protecting and intestinal flora-balancing effects, and the best effect was achieved at an additive dose of 0.2%.

Microplastics, a new type of emerging pollutant, is ubiquitous in terrestrial and water environments. Microplastics have become a growing concern due to their impacts on the environment, animal, and human health. Birds also suffer from microplastics contamination. In this study, we examined the toxic effects of polystyrene microplastics (PS-MPs) exposure on physical barrier, microbial community, and immune function in the cecum of a model bird species-Japanese quail (Coturnix japonica). The one-week-old birds were fed on environmentally relevant concentrations of 20 µg/kg, 400 µg/kg, and 8 mg/kg PS-MPs in the diet for 5 weeks. The results showed that microplastics could cause microstructural damages characterized by lamina propria damage and epithelial cell vacuolation and ultrastructural injuries including microvilli breakage and disarrangement as well as mitochondrial vacuolation in the cecum of quails. In particular, blurry tight junctions, wider desmosomes spacing, and gene expression alteration indicated cecal tight junction malfunction. Moreover, mucous layer breakdown and mucin decrease indicated that chemical barrier was disturbed by PS-MPs. PS-MPs also changed cecal microbial diversity. In addition, structural deformation of cecal tonsils and increasing proinflammatory cytokines suggested cecal immune disorder and inflammation responses by PS-MPs exposure. Our results suggested that microplastics negatively affected digestive system and might pose great health risks to terrestrial birds.

UNASSIGNED: Disturbed intestinal microbiota has been implicated in the inflammatory microenvironment of the colon, which usually results in ulcerative colitis (UC). Given the limitations of these drugs, it is important to explore alternative means of protecting the gut health from UC. This study aimed to investigate the potential of polysaccharides as beneficial nutrients in the regulation of the gut microbiota, which determines the inflammatory microenvironment of the colon.
UNASSIGNED: Mice were treated with dextran sulfate sodium (DSS) to evaluate the effects and mechanisms of Lycium barbarum polysaccharide (LBP) in remodeling the inflammatory microenvironment and improving gut health. Body weight and disease activity indices were monitored daily. Hematoxylin and eosin staining was used to analyze colon dynamics. The levels of inflammatory indicators and expression of MUC-2, claudin-1, ZO-1, and G-protein-coupled receptor 5 (TGR5) were determined using assay kits and immunohistochemistry, respectively. 16S rRNA high-throughput sequencing of the intestinal microbiota and liquid chromatography-tandem mass spectrometry for related bile acids were used.
UNASSIGNED: LBP significantly improved the colonic tissue structure by upregulating MUC-2, claudin-1, and ZO-1 protein expression. The bacterial genus Dubosiella was dominant in healthy mice, but significantly decreased in mice treated with DSS. LBP rehabilitated Dubosiella in the sick guts of DSS mice to a level close to that of healthy mice. The levels of other beneficial bacterial genera Akkermansia and Bifidobacterium were also increased, whereas those of the harmful bacterial genera Turicibacter, Clostridium_sensu_stricto_1, Escherichia-Shigella, and Faecalibaculum decreased. The activity of beneficial bacteria promoted the bile acids lithocholic and deoxycholic acids in mice with UC, which improved the gut barrier function through the upregulation of TGR5.
UNASSIGNED: The inflammatory microenvironment in the gut is determined by the balance of the gut microbiota. LBP showed great potential as a beneficial nutrient for rehabilitating Dubosiella which is dominant in the gut of healthy mice. Nutrient-related LBP may play an important role in gut health management.

Parkinson\'s disease (PD) is a neurodegenerative disorder commonly accompanied by gut dysfunction. EA has shown anti-inflammatory and neuroprotective effects. Here, we aim to explore whether EA can treat Parkinson\'s disease by restoring the intestinal barrier and modulating NLRP3 inflammasome. We applied 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model and EA at the GV16, LR3, and ST36 for 12 consecutive days. The open-field test results indicated that EA alleviated depression and behavioral defects, upregulated the expressions of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), and blocked the accumulation of α-synuclein (α-syn) in the midbrain. Moreover, EA blocked the damage to intestinal tissues of PD mice, indicative of suppressed NLRP3 inflammasome activation and increased gut barrier integrity. Notably, the antibiotic-treated mouse experiment validated that the gut microbiota was critical in alleviating PD dyskinesia and intestinal inflammation by EA. In conclusion, this study suggested that EA exhibited a protective effect against MPTP-induced PD by alleviating behavioral defects, reversing the block of motor dysfunction, and improving the gut barrier by modulating intestinal NLRP3 inflammasome. Above all, this study could provide novel insights into the pathogenesis and therapy of PD.

Resistant starch serves as a prebiotic in the large intestine, aiding in the maintenance of a healthy intestinal environment and mitigating associated chronic illnesses. This study aimed to investigate the impact of resistant starch-enriched brown rice (RBR) on intestinal health and functionality. We assessed changes in resistant starch concentration, structural alterations, and branch chain length distribution throughout the digestion process using an in vitro model. The efficacy of RBR in the intestinal environment was evaluated through analyses of its prebiotic potential, effects on intestinal microbiota, and intestinal function-related proteins in obese animals fed a high-fat diet. RBR exhibited a higher yield of insoluble fraction in both the small and large intestines compared to white and brown rice. The total digestible starch content decreased, while the resistant starch content significantly increased during in vitro digestion. Furthermore, RBR notably enhanced the growth of four probiotic strains compared to white and brown rice, displaying higher proliferation activity than the positive control, FOS. Notably, consumption of RBR by high-fat diet-induced obese mice suppressed colon shortening, increased Bifidobacteria growth, and improved intestinal permeability. These findings underscore the potential prebiotic and gut health-promoting attributes of RBR, offering insights for the development of functional foods aimed at preventing gastrointestinal diseases.

Human breast milk promotes maturation of the infant gastrointestinal barrier, including the promotion of mucus production. In the quest to produce next generation infant milk formula (IMF), we have produced IMF by membrane filtration (MEM-IMF). With a higher quantity of native whey protein, MEM-IMF more closely mimics human breast milk than IMF produced using conventional heat treatment (HT-IMF). After a 4-week dietary intervention in young pigs, animals fed a MEM-IMF diet had a higher number of goblet cells, acidic mucus and mucin-2 in the jejunum compared to pigs fed HT-IMF (P < 0.05). In the duodenum, MEM-IMF fed pigs had increased trypsin activity in the gut lumen, increased mRNA transcript levels of claudin 1 in the mucosal scrapings and increased lactase activity in brush border membrane vesicles than those pigs fed HT-IMF (P < 0.05). In conclusion, MEM-IMF is superior to HT-IMF in the promotion of mucus production in the young gut.