The gut microbiota can act as a buffer against changes in energy and food availability and adapt plastically to fluctuations in the host's diet. However, it is unknown how changes in the gut microbiome with the seasons impact microbial metabolism and the accessibility of nutrients to hosts. The study utilized 16S rRNA and UHPLC-MS/MS approaches to examine seasonal fecal metabolome variations in the captive Yangtze finless porpoises (YFPs) to determine if these variations are linked to nutrient intake or gut microbiome composition changes. The YFPs were mostly fed a frozen and live fish diet, with different food intakes yearly. We found that gut microbial diversity remained constant, but community structure varied seasonally. Firmicutes and Cyanobacteria were higher in winter, Actinobacteria in spring and fall, and proteobacteria in summer. The genus Paeniclostridium was significantly higher in the spring season, Romboutsia and Clostridium_sensu_stricto_13 were significantly higher in the summer, while Terrisporobacter and Macrococcus were significantly higher in the fall group. The study reported that seasonal dietary variation significantly impacted the fecal metabolome by affecting the metabolism, including energy, amino acid, carbohydrate, and nucleotide metabolism of the captive YFP. Moreover, significant correlations between metabolome and microbiome were found, and these correlations may indicate that the captive YFP has adapted to cope with dietary variations and enhance energy acquisition. These findings improve our knowledge of the link between microbiota, diet, metabolites, and the physiology of the host and suggest that gut microbial populations may adapt continuously to changes in diet.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and emotional instability, primarily resulting from the abnormal accumulation of mutant huntingtin protein. Growing research highlights the role of intestinal microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), in modulating HD progression. SCFAs, including acetate, propionate, and butyrate, are produced by gut bacteria through dietary fiber fermentation and are recognized for their neuroprotective properties. Evidence suggests that SCFAs regulate neuroinflammation, neuronal communication, and metabolic functions within the central nervous system (CNS). In HD, these compounds may support neuronal health, reduce oxidative stress, and enhance blood-brain barrier (BBB) integrity. Their mechanisms of action involve binding to G-protein-coupled receptors (GPCRs) and modulating gene expression through epigenetic pathways, underscoring their therapeutic potential. This analysis examines the significance of SCFAs in HD, emphasizing the gut-brain axis and the benefits of dietary interventions aimed at modifying gut microbiota composition and promoting SCFA production. Further research into these pathways may pave the way for novel HD management strategies and improved therapeutic outcomes.

Chronic gut inflammation and dysbiosis contribute significantly to colorectal cancer (CRC) development. Shaoyao decoction (SYD) is a well-established Chinese medicine prescription. Besides ameliorating CRC via anti-inflammatory effects, SYD modulates gut microbiota (GM) to improve inflammatory responses in ulcerative colitis (UC). However, whether and how SYD suppresses CRC by regulating GM remains largely unknown.

SD rats were orally administered SYD for 7 days to obtain medicated serum. We utilized liquid chromatography-mass spectrometry (LC-MS) analysis, GeneCards, DisGeNET, and SwissTargetPrediction databases to analyze blank and SYD-medicated rat serum, comparing the findings with those of SYD aqueous extract in previous studies to identify SYD circulating compounds/components with predictable target genes. Using network pharmacology, the potential active compounds and corresponding hub genes associated with modulating GM to suppress CRC were selected for molecular docking. In vivo experiments, a CRC transplantation tumor model was established in BALB/c mice using CT26 cells, with SYD gavage for 14 days. To investigate the mechanism of SYD-regulated GM against CRC, HE and IHC staining, Western blotting, and 16S rRNA sequencing were employed.

LC-MS identified 26 SYD compounds with computationally predicted target genes. Network pharmacology prioritized 13 compounds targeting 8 inflammation/immunity-related genes (IL-17/TNF pathways), validated by molecular docking. In vivo experiments, SYD dose-dependently suppressed tumor growth (p < 0.05, medium/high doses), as confirmed by HE staining and IHC analysis of Ki-67. Notably, SYD potentially delayed CRC liver metastasis and alleviated hepatic injury in tumor-bearing mice. Western blotting demonstrated SYD's inhibition of the IL-17/TNF/NF-κB axis, aligning with computational predictions. 16S rRNA sequencing revealed SYD-enriched Akkermansia and GM structural shifts, mechanistically linking microbiota remodeling to anti-tumor efficacy.

SYD combats CRC via dual modulation of IL-17/TNF/NF-κB signaling and GM ecosystems (e.g., Akkermansia enrichment). This microbiota-immune crosstalk positions SYD as a potential adjunct to conventional therapies, particularly for CRC patients with dysbiosis.

The holobiome is an interconnected network of microbial ecosystems spanning soil, plants, animals, humans, and the environment. Microbial interactions drive nutrient cycling, pathogen suppression, and climate regulation. Soil microbiomes facilitate carbon sequestration and enhance soil fertility, while marine microbiomes contribute to carbon capture and climate stability. However, industrial agriculture, extensive herbicide use, antibiotic overuse, and climate change threaten microbial diversity, leading to ecosystem and health disruptions. Probiotic interventions help to restore microbial balance. In human health, probiotics support gut microbiota diversity, reduce inflammation, and regulate metabolism. In agriculture, soil probiotics enhance microbial diversity, improve nutrient cycling, and degrade contaminants, increasing crop yields and soil health. Case studies show that microbial inoculants effectively remediate degraded soils and enhance nutrient uptake. Artificial intelligence is transforming microbiome research by enabling predictive modeling, precision probiotic design, and microbial consortia optimization. Interdisciplinary collaboration and supportive policies are essential for restoring microbial equilibria, ensuring ecosystem resilience, and promoting long-term sustainability. The integration of artificial intelligence, clinical research, and sustainable practices is crucial for advancing holobiome science. The holobiome framework underscores the need for interdisciplinary collaboration to address global challenges, bridging environmental sustainability, agriculture, and public health for a resilient future.

Oil supplements have various benefits for metabolism, particularly Sacha inchi oil (SI), which is rich in polyunsaturated fatty acids (PUFAs) such as ω-3 and fat-soluble vitamins. However, the impacts of oil supplements on gut health remain unclear. The aim of this study was to compare the effects of an SI supplement with those of lard oil (LO), known for its high saturated fatty acid content, and a normal diet on gut health in male Sprague Dawley rats for 12 consecutive weeks. Fecal DNA was used to assess gut microbiota diversity and species abundance, diversity, and function prediction. Colon tissue from each rat was examined for colon crypt depth and histology. Rats administered the LO supplement exhibited higher dysbiosis than those administered the SI supplement, with the LO supplement influencing the relative abundance of various bacteria at the genus level. A KEGG analysis was conducted to examine the effects on metabolic pathways, revealing that the SI supplement promoted carbohydrate metabolism while reducing immune system activity. In contrast, the LO supplement increased replication, repair, and translation activities. A histological analysis of the colon tissues showed no significant alterations in crypt depth or lesions in all groups, indicating that neither supplement induced adverse structural changes in the gut. The results of this study suggest that SI supplementation modulates the gut microbiota, thereby enhancing gut health and metabolic function.

Oral administration of acetic acid, a short-chain fatty acid, has been shown to efficiently reduce obesity and insulin resistance in both experimental animals and humans. The anti-atherosclerotic effect of acetate is expected owing to its anti-inflammatory and anti-oxidative stress characteristics; however, this remains to be fully understood.

For 12 weeks, apolipoprotein E-deficient mice were administered 0.6 % sodium acetate water or vehicle water. Plaque formation and progression were investigated using histological analysis of dissected aortic root sections. Flow cytometry and gene expression analyses were employed to assess plaque macrophage characteristics and functional states. In vitro tests were performed on mouse peritoneal primary macrophages and bone marrow-derived macrophages isolated from wild-type or GPR43-deficient mice.

Atherosclerotic plaque formation was inhibited in acetate-treated ApoE-deficient mice, and AMPK activation was directly validated in plaque macrophages. Acetate inhibited macrophage proliferation, reactive oxygen species production, and pro-inflammatory molecule expression, all of which were reversed by AMPK inhibition. Bone marrow transplantation study revealed the role of GPR43-mediated AMPK activation by acetic acid in anti-atherosclerotic effect.

Oral acetate administration suppressed arteriosclerosis formation and progression in ApoE-deficient mice. Acetate inhibited macrophage proliferation, inflammatory cytokine release, and reactive oxygen species production via GPR43-mediated AMPK activation in macrophages, ameliorating plaque formation and progression.

Due to highly personalized biological and lifestyle characteristics, different individuals may have different metabolite responses to specific foods and nutrients. In particular, the gut microbiota, a collection of trillions of microorganisms living in the gastrointestinal tract, is highly personalized and plays a key role in the metabolite responses to foods and nutrients. Accurately predicting metabolite responses to dietary interventions based on individuals' gut microbial compositions holds great promise for precision nutrition. Existing prediction methods are typically limited to traditional machine learning models. Deep learning methods dedicated to such tasks are still lacking. Here we develop a method McMLP (Metabolite response predictor using coupled Multilayer Perceptrons) to fill in this gap. We provide clear evidence that McMLP outperforms existing methods on both synthetic data generated by the microbial consumer-resource model and real data obtained from six dietary intervention studies. Furthermore, we perform sensitivity analysis of McMLP to infer the tripartite food-microbe-metabolite interactions, which are then validated using the ground-truth (or literature evidence) for synthetic (or real) data, respectively. The presented tool has the potential to inform the design of microbiota-based personalized dietary strategies to achieve precision nutrition.

Atherosclerosis (AS) is a cardiovascular disease caused by excessive accumulation of lipids in arterial walls. In this study, we developed an AS model in ApoE-/- mice using a high-fat, high-cholesterol diet and investigated the anti-AS mechanism of aged garlic oligosaccharides (AGOs) by focusing on the gut microbiota. Results revealed that AGOs exhibited significant anti-AS effects, reduced trimethylamine N-oxide levels from 349.9 to 189.2 ng/mL, and reduced aortic lipid deposition from 31.7 % to 9.5 %. AGOs significantly increased the levels of short-chain fatty acids in feces, in which acetic, propionic, and butyric acids were increased from 1.580, 0.364, and 0.469 mg/g to 2.233, 0.774, and 0.881 mg/g, respectively. An analysis of the gut microbiota indicated that AGOs restored alpha and beta diversity, decreased the Firmicutes/Bacteroidetes ratio, and promoted the dominance of the genus Akkermansia. A metagenomic analysis revealed that AGOs alleviated AS through the ABC transporter pathway and the lipopolysaccharide biosynthesis pathway.

Camel milk is a valuable food source with unique nutritional properties and potential health benefits. This study investigated the influence of high dietary salt on milk composition and fatty acid (FA) profile as well as insulin regulation in dairy camels. Twelve multiparous female camels were used in a crossover design with two treatments: control concentrate (CON; 1.3% salt) and high-salt concentrate (SAL; 3.9% salt). Each period lasted 3 weeks, with camels switched between treatments in the second period. The measured variables included milk yield, milk composition, blood metabolites, and insulin levels in blood and milk. The SAL group exhibited higher (p < 0.01) water consumption. Nevertheless, milk yield and composition (fat, protein, lactose) remained unaffected. Notably, SAL camels had elevated blood insulin levels (p < 0.05) compared to the CON group, suggesting enhanced pancreatic activity possibly driven by osmotic balance changes. Milk FA profiles revealed a reduction in unsaturated fatty acids (UFA, p < 0.04), particularly monounsaturated (MUFA, p < 0.05) and odd-chain fatty acids (OCFA, p < 0.05). Furthermore, lipid quality indices such as the atherogenic index (p < 0.01) and the hypocholesterolemic/hypercholesterolemic FA ratio (h/H, p < 0.01) indicated a less favorable milk fat profile in the SAL group. These findings suggest that while moderate salt supplementation may not negatively impact milk yield in dairy camels, it alters both metabolic and milk fat composition variables, with potential implications for the nutritional quality of milk.

This study sought to determine if dietary macronutrient consumption and the low-carbohydrate diet (LCD) score were linked to rheumatoid arthritis (RA).

Participants ≥ 20 years were analyzed from the National Health and Nutrition Examination Survey (NHANES) 2011-2016. LCD score was calculated by summing the 11 quantiles values of the percentages of energy derived from carbohydrate, protein, and fat. Weighted logistic regression, eXtreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM) models were used to explore the relationship between LCD score, dietary macronutrient intake, and RA. Propensity score matching (PSM) were applied for sensitivity analysis.

Ultimately, 8118 participants (RA: 499, without RA: 7619) were analyzed. After fully adjusting for confounders, a negative association was found between the LCD score and the presence of RA [OR (95% CI), 0.97 (0.96, 0.99)]. A higher LCD score was also negatively associated with a lower likelihood of RA based on a categorical model. Among macronutrients, participants in the third and fourth quartiles had significantly increased odds of RA compared with the lowest carbohydrate intake. Regarding protein intake, individuals in the highest quartile of percentage of energy from protein had a 46% lower presence of RA compared with the lowest reference group. The relative importance of the LCD score on RA was determined based on XGBoost and LightGBM models. Moreover, the association between the LCD score, dietary macronutrient intake, and RA presence remained substantial after PSM.

LCD score was negatively associated with odds of RA in US adults. Moreover, a correlation was found between a lower likelihood of RA and high protein, and low carbohydrate consumption. Key Points • A significant negative association was found between LCD score and RA presence. • Machine learning models revealed the LCD score was a significant predictor of the presence of RA. • Low carbohydrate intake and high protein intake were correlated with a lower odds of RA.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to major global health concern. However, the focus on immediate effects was assumed as the tip of iceberg due to the symptoms following acute infection, which was defined as post-acute COVID-19 syndrome (PACS). Gut microbiota alterations even after disease resolution and the gastrointestinal symptoms are the key features of PACS. Gut microbiota and derived metabolites disorders may play a crucial role in inflammatory and immune response after SARS-CoV-2 infection through the gut-lung axis. Diet is one of the modifiable factors closely related to gut microbiota and COVID-19. In this review, we described the reciprocal crosstalk between gut and lung, highlighting the participation of diet and gut microbiota in and after COVID-19 by destroying the gut barrier, perturbing the metabolism and regulating the immune system. Therefore, bolstering beneficial species by dietary supplements, probiotics or prebiotics and fecal microbiota transplantation (FMT) may be a novel avenue for COVID-19 and PACS prevention. This review provides a better understanding of the association between gut microbiota and the long-term consequences of COVID-19, which indicates modulating gut dysbiosis may be a potentiality for addressing this multifaceted condition.

Obesity is a chronic, multifactorial disease characterized by persistent low-grade tissue and systemic inflammation. Fat accumulation in adipose tissue (AT) leads to stress and dysfunctional adipocytes, along with the infiltration of immune cells, which initiates and sustains inflammation. Neutrophils are the first immune cells to infiltrate AT during high-fat diet (HFD)-induced obesity. Emerging evidence suggests that the formation and release of neutrophil extracellular traps (NETs) play a significant role in the progression of obesity and related diseases. Additionally, obesity is associated with an imbalance in gut microbiota and increased intestinal barrier permeability, resulting in the translocation of live bacteria, bacterial deoxyribonucleic acid (DNA), lipopolysaccharides (LPS), and pro-inflammatory cytokines into the bloodstream and AT, thereby contributing to metabolic inflammation. Recent research has also shown that short-chain fatty acids (SCFAs), produced by gut microbiota, can influence various functions of neutrophils, including their activation, migration, and the generation of inflammatory mediators. This review comprehensively summarizes recent advancements in understanding the role of neutrophils and NET formation in the pathophysiology of obesity and related disorders while also focusing on updated potential therapeutic approaches targeting NETs based on studies conducted in humans and animal models.

Atherosclerosis (AS) is an inflammatory arterial disorder that occurs due to the deposition of the excessive lipoprotein under the artery intima, mainly including low-density lipoprotein and other apolipoprotein B-containing lipoproteins. G protein-coupled receptors (GPCRs) play a crucial role in transmitting signals in physiological and pathophysiological conditions. GPCRs recognize inflammatory mediators, thereby serving as important players during chronic inflammatory processes. It has been demonstrated that free fatty acids can function as ligands for various GPCRs, such as free fatty acid receptor (FFAR)1/GPR40, FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120, and the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). This review discusses GPR43 and its ligands in the pathogenesis of AS, especially focusing on its distinct role in regulating chronic vascular inflammation, inhibiting oxidative stress, ameliorating endothelial dysfunction and improving dyslipidemia. It is hoped that this review may provide guidance for further studies aimed at GPR43 as a promising target for drug development in the prevention and therapy of AS.

Immunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies.

Olfactory receptor 2 (Olfr2) has been identified in a minimum of 30% of vascular macrophages, and its depletion was shown to reduce atherosclerosis progression. Mononuclear phagocytes, including monocytes and macrophages within the vessel wall, are major players in atherosclerosis. Single-cell RNA sequencing studies revealed that atherosclerotic artery walls encompass several monocytes and vascular macrophages, defining at least nine distinct subsets potentially serving diverse functions in disease progression. This study investigates the functional phenotype and ontogeny of Olfr2-expressing vascular macrophages in atherosclerosis.

Olfr2+ macrophages rapidly increase in Apoe-/- mice's aorta when fed a Western diet (WD). Mass cytometry showed that Olfr2+ cells are clustered within the CD64 high population and enriched for CD11c and Ccr2 markers. Olfr2+ macrophages express many pro-inflammatory cytokines, including Il1b, Il6, Il12, and Il23, and chemokines, including Ccl5, Cx3cl1, Cxcl9, and Ccl22. By extracting differentially expressed genes from bulk RNA sequencing (RNA-seq) of Olfr2+ vs. Olfr2- macrophages, we defined a signature that significantly mapped to single-cell data of plaque myeloid cells, including monocytes, subendothelial MacAir, and Trem2Gpnmb foamy macrophages. By adoptive transfer experiments, we identified that Olfr2 competent monocytes from CD45.1Apoe-/-Olfr2+/+ mice transferred into CD45.2Apoe-/-Olfr2-/- recipient mice fed WD for 12 weeks, accumulate in the atherosclerotic aorta wall already at 72 h, and differentiate in macrophages. Olfr2+ macrophages showed significantly increased BrdU incorporation compared to Olfr2- macrophages. Flow cytometry confirmed that at least 50% of aortic Olfr2+ macrophages are positive for BODIPY staining and have increased expression of both tumour necrosis factor and interleukin 6 compared to Olfr2- macrophages. Gene set enrichment analysis of the Olfr2+ macrophage signature revealed a similar enrichment pattern in human atherosclerotic plaques, particularly within foamy/TREM2hi-Mφ and monocytes.

In summary, we conclude that Olfr2+ macrophages in the aorta originate from monocytes and can accumulate at the early stages of disease progression. These cells can undergo differentiation into MacAir and Trem2Gpnmb foamy macrophages, exhibiting proliferative and pro-inflammatory potentials. This dynamic behaviour positions them as key influencers in shaping the myeloid landscape within the atherosclerotic plaque.

The intestinal microbiota is a complex ecosystem where the microbial community (including bacteria) can metabolize available substrates via metabolic pathways specific to each species, often related in symbiotic relations. As a consequence of using available substrates and microbial growth, specific beneficial metabolites can be produced. When this reflects the health benefits for the host, these substrates can be categorized as prebiotics. Given that most prebiotic candidates must have a low molecular weight to be further metabolized by the microbiota, the role in the preliminary biological pretreatment is crucial. To provide proper substrates to the intestinal microbiota, a strategy could be to decrease the complexity of polysaccharides and reduce the levels of polymerization to low molecular weight for the target molecules, driving better solubilization and the consequent metabolic use by intestinal bacteria. When high molecular weight pectin is degraded (partially depolymerized), its solubility increases, thereby improving its utilization by gut microbiota. With regards to application, prebiotics have well-documented advantages when applied as food additives, as they improve gut health and can enhance drug effects, all shown by in vitro, in vivo, and clinical trials. In this review, we aim to provide systematic evidence for the mechanisms of action and the modulation of gut microbiota by the pectin-derived oligosaccharides produced by decreasing overall molecular weight after physical and/or chemical treatments and to compare with other types of prebiotics.

Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS.

ApoE-/- mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content.

The results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality.

These findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, short-chain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis.

The increasing prevalence of individuals affected by bone pathologies globally has sparked catastrophic concerns. Ankylosing spondylitis, osteoporosis, rheumatoid arthritis, osteoarthritis, and fractures alone impact an estimated 1.71 billion people worldwide. The gut microbiota plays a crucial role in interacting with the host through the synthesis of a diverse range of metabolites called gut-associated metabolites (GAMs), which originate from external dietary substrates or endogenous host compounds. Many metabolic disorders have been linked to alterations in the gut microbiota's activity and composition. The development of metabolic illnesses has been linked to certain microbiota-derived metabolites, such as branched-chain amino acids, bile acids, short-chain fatty acids, tryptophan, trimethylamine N-oxide, and indole derivatives. Moreover, the modulation of gut microbiota through biotics (prebiotics, probiotics and postbiotics) presents a promising avenue for therapeutic intervention. Biotics selectively promote the growth of beneficial gut bacteria, thereby enhancing the production of GAMs with potential beneficial effects on bone metabolism. Understanding the intricate interplay between GAMs, and bone-associated genes through molecular informatics holds significant promise for early diagnosis, prognosis, and novel treatment strategies for various bone disorders.

Epidemiological evidence suggests that fruit and vegetable intake significantly positively affects cardiovascular health. Since vegetable juice is more accessible than raw vegetables, it attracts attention as a health functional food for circulatory diseases. Therefore, this study measured blood lipids, antioxidants, blood circulation indicators, and changes in the microbiome to confirm the effect of organic vegetable mixed juice (OVJ) on improving blood circulation. This 4-week, randomized, double-blinded, placebo-controlled study involved adult men and women with borderline total cholesterol (TC) and low-density lipoprotein (LDL) levels. As a result, blood lipid profile indicators, such as TC, triglycerides, LDL cholesterol, and apolipoprotein B, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. Additionally, the antioxidant biomarker superoxide dismutase increased (p < 0.05). In contrast, systolic and diastolic blood viscosities, as blood circulation-related biomarkers, decreased (p < 0.05) in the OVJ group compared with those in the placebo group. After the intervention, a fecal microbiome analysis confirmed differences due to changes in the intestinal microbiome composition between the OVJ and placebo groups. In conclusion, our research results confirmed that consuming OVJ improves blood circulation by affecting the blood lipid profile, antioxidant enzymes, and microbiome changes.

Due to highly personalized biological and lifestyle characteristics, different individuals may have different metabolite responses to specific foods and nutrients. In particular, the gut microbiota, a collection of trillions of microorganisms living in the gastrointestinal tract, is highly personalized and plays a key role in the metabolite responses to foods and nutrients. Accurately predicting metabolite responses to dietary interventions based on individuals' gut microbial compositions holds great promise for precision nutrition. Existing prediction methods are typically limited to traditional machine learning models. Deep learning methods dedicated to such tasks are still lacking. Here we develop a method McMLP (Metabolite response predictor using coupled Multilayer Perceptrons) to fill in this gap. We provide clear evidence that McMLP outperforms existing methods on both synthetic data generated by the microbial consumer-resource model and real data obtained from six dietary intervention studies. Furthermore, we perform sensitivity analysis of McMLP to infer the tripartite food-microbe-metabolite interactions, which are then validated using the ground-truth (or literature evidence) for synthetic (or real) data, respectively. The presented tool has the potential to inform the design of microbiota-based personalized dietary strategies to achieve precision nutrition.

Experimental diets were formulated including the suitable lipid level (10%, PC), the high-lipid level (16%, HL), and HL containing sodium acetate diets (HS). Three diets were fed golden pompano (Trachinotus ovatus) (initial body weight: 12.88 ± 0.03 g) for 8 weeks. The results showed HL diets significantly increased hepatosomatic index (HSI) and abdominal fat percentage (ASF), aggravated liver lipid deposition, and caused blood metabolic disorder and liver damage (P < 0.05). Moreover, the fish fed HL diets significantly decreased intestinal villus number (VN) and muscular layer thickness (MLT) (P < 0.05), accompanied with an increased trend in the relative abundance of intestinal pathogenic bacteria such as Mycoplasma and Photobacterium. However, the fish fed HS diets significantly decreased the HSI and AFP, relieved hepatic lipid deposition, improved blood and liver metabolism, and intestinal morphology in comparison to the fish fed HL diets (P < 0.05). More importantly, sodium acetate addition improved intestinal microbiota by inhibiting the proportion of pathogens (Mycoplasma and Vibrio) and increasing the abundance of probiotics (Bacteroidales_S24-7_group_norank, Cetobacterium, Bacteroides, and Lachnospiraceae_NK4A136_group). Furthermore, there was a strong correlation between these bacteria (Mycoplasma, Vibrio, Lachnospiraceae_NK4A136_group, Bacteroidales_S24-7_group_norank, Bacteroides, and Cetobacterium) and main physiological indices. In conclusion, sodium acetate improved blood performance, alleviated hepatic lipid deposition induced by HL diets, and boosted the growth and intestinal health for golden pompano.

Cardiovascular diseases (CVDs) represent a significant global health challenge, underscoring the need for innovative approaches to prevention and treatment. Recent years have seen a surge in interest in unraveling the complex relationship between the gut microbiome and cardiovascular health. This article delves into current research on the composition, diversity, and impact of the gut microbiome on CVD development. Recent advancements have elucidated the profound influence of the gut microbiome on disease progression, particularly through key mediators like Trimethylamine-N-oxide (TMAO) and other microbial metabolites. Understanding these mechanisms reveals promising therapeutic targets, including interventions aimed at modulating the gut microbiome's interaction with the immune system and its contribution to endothelial dysfunction. Harnessing this understanding, personalized medicine strategies tailored to individuals' gut microbiome profiles offer innovative avenues for reducing cardiovascular risk. As research in this field continues to evolve, there is vast potential for transformative advancements in cardiovascular medicine, paving the way for precision prevention and treatment strategies to address this global health challenge.

Gulf War Illness (GWI) is a debilitating condition marked by chronic fatigue, cognitive problems, pain, and gastrointestinal (GI) complaints in veterans who were deployed to the 1990-1991 Gulf War. Fatigue, GI complaints, and other chronic symptoms continue to persist more than 30 years post-deployment. Several potential mechanisms for the persistent illness have been identified and our prior pilot study linked an altered gut microbiome with the disorder. This study further validates and builds on our prior preliminary findings of host gut microbiome dysbiosis in veterans with GWI. Using stool samples and Multidimensional Fatigue Inventory (MFI) data from 89 GW veteran participants (63 GWI cases and 26 controls) from the Boston biorepository, recruitment, and integrative network (BBRAIN) for Gulf War Illness, we found that the host gut bacterial signature of veterans with GWI showed significantly different Bray-Curtis beta diversity than control veterans. Specifically, a higher Firmicutes to Bacteroidetes ratio, decrease in Akkermansia sp., Bacteroides thetaiotamicron, Bacteroides fragilis, and Lachnospiraceae genera and increase in Blautia, Streptococcus, Klebsiella, and Clostridium genera, that are associated with gut, immune, and brain health, were shown. Further, using MaAsLin and Boruta algorithms, Coprococcus and Eisenbergiella were identified as important predictors of GWI with an area under the curve ROC predictive value of 74.8%. Higher self-reported MFI scores in veterans with GWI were also significantly associated with an altered gut bacterial diversity and species abundance of Lachnospiraceae and Blautia. These results suggest potential therapeutic targets for veterans with GWI that target the gut microbiome and specific symptoms of the illness.

Background: Available evidence points to a possible role of Short Chain Fatty Acids (SCFAs) in mood disorders. This is the first systematic review to map the associations between SCFA levels and mood disorder symptoms.Methods: Following the PRISMA guidelines, the databases PubMed, Embase, and PsycINFO were searched for studies that assessed SCFA levels in human populations with mood disorder symptoms, or animal models of mood disorder. Risk of bias was assessed by the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) checklist.Results: 19 studies were included and could be divided into animal (n=8) and human studies (n=11), with the animal studies including 166 animals and 100 controls, and the human studies including 662 participants and 330 controls. The studies were characterized by heterogeneity and methodological challenges on multiple parameters, limiting the validity and transferability of findings. Notably, only two of the clinical studies assessed the presence of mood disorder with diagnostic criteria, and no studies of mania or bipolar disorder met the inclusion criteria.Discussion: Despite significant methodological limitations, associations between SCFA levels and depressive symptoms were reported in most of the studies. However, the direction of these associations and the specific SCFAs identified varied. The quantification of SCFA levels in mood disorders is an emerging yet sparsely studied research field. Although there is some evidence suggesting a link between SCFAs and depressive symptoms, the directionality of effects and mechanisms are unclear and the relation to manic symptoms is uninvestigated.

Recent advancements in genomics, transcriptomics, and metabolomics have significantly advanced our understanding of the human gut microbiome and its impact on the efficacy and toxicity of anti-cancer therapeutics, including chemotherapy, immunotherapy, and radiotherapy. In particular, prebiotics, probiotics, and postbiotics are recognized for their unique properties in modulating the gut microbiota, maintaining the intestinal barrier, and regulating immune cells, thus emerging as new cancer treatment modalities. However, clinical translation of microbiome-based therapy is still in its early stages, facing challenges to overcome physicochemical and biological barriers of the gastrointestinal tract, enhance target-specific delivery, and improve drug bioavailability. This review aims to highlight the impact of prebiotics, probiotics, and postbiotics on the gut microbiome and their efficacy as cancer treatment modalities. Additionally, we summarize recent innovative engineering strategies designed to overcome challenges associated with oral administration of anti-cancer treatments. Moreover, we will explore the potential benefits of engineered gut microbiome-modulating approaches in ameliorating the side effects of immunotherapy and chemotherapy.

Cardiovascular disease (CVD) is a global health concern. Circadian medicine improves cardiovascular care by aligning treatments with our body's daily rhythms and their underlying cellular circadian mechanisms. Time-based therapies, or chronotherapies, show special promise in clinical cardiology. They optimize treatment schedules for better outcomes with fewer side effects by recognizing the profound influence of rhythmic body cycles. In this review, we focus on three chronotherapy areas (medication, light, and meal timing) with potential to enhance cardiovascular care. We also highlight pioneering research in the new field of rest, the gut microbiome, novel chronotherapies for hypertension, pain management, and small molecules that targeting the circadian mechanism.

Olfactory receptors (ORs) are G protein coupled receptors (GPCRs) with seven transmembrane domains that bind to specific exogenous chemical ligands and transduce intracellular signals. They constitute the largest gene family in the human genome. They are expressed in the epithelial cells of the olfactory organs and in the non-olfactory tissues such as the liver, kidney, heart, lung, pancreas, intestines, muscle, testis, placenta, cerebral cortex, and skin. They play important roles in the normal physiological and pathophysiological mechanisms. Recent evidence has highlighted a close association between ORs and several metabolic diseases. Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally. Furthermore, ORs play an essential role in the development and functional regulation of the cardiovascular system and are implicated in the pathophysiological mechanisms of CVDs, including atherosclerosis (AS), heart failure (HF), aneurysms, and hypertension (HTN). This review describes the specific mechanistic roles of ORs in the CVDs, and highlights the future clinical application prospects of ORs in the diagnosis, treatment, and prevention of the CVDs.

The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N -oxide (TMAO), short-chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449-5490, 2024.

The lymphatic fluid is the conduit by which part of the tissue "omics" is transported to the draining lymph node for immunosurveillance. Following cannulation of the pre-nodal cervical and mesenteric afferent lymphatics, herein we investigate the lymph proteomic composition, uncovering that its composition varies according to the tissue of origin. Tissue specificity is also reflected in the dendritic cell-major histocompatibility complex class II-eluted immunopeptidome harvested from the cervical and mesenteric nodes. Following inflammatory disruption of the gut barrier, the lymph antigenic and inflammatory loads are analyzed in both mice and subjects with inflammatory bowel diseases. Gastrointestinal tissue damage reflects the lymph inflammatory and damage-associated molecular pattern signatures, microbiome-derived by-products, and immunomodulatory molecules, including metabolites of the gut-brain axis, mapped in the afferent mesenteric lymph. Our data point to the relevance of the lymphatic fluid to probe the tissue-specific antigenic and inflammatory load transported to the draining lymph node for immunosurveillance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.

Gut microbiota interacts with host epithelial cells and regulates many physiological functions such as genetics, epigenetics, metabolism of nutrients, and immune functions. Dietary factors may also be involved in the etiology of colorectal cancer (CRC), especially when an unhealthy diet is consumed with excess calorie intake and bad practices like smoking or consuming a great deal of alcohol. Bacteria including Fusobacterium nucleatum, Enterotoxigenic Bacteroides fragilis (ETBF), and Escherichia coli (E. coli) actively participate in the carcinogenesis of CRC. Gastrointestinal tract with chronic inflammation and immunocompromised patients are at high risk for CRC progression. Further, the gut microbiota is also involved in Geno-toxicity by producing toxins like colibactin and cytolethal distending toxin (CDT) which cause damage to double-stranded DNA. Specific microRNAs can act as either tumor suppressors or oncogenes depending on the cellular environment in which they are expressed. The current review mainly highlights the role of gut microbiota in CRC, the mechanisms of several factors in carcinogenesis, and the role of particular microbes in colorectal neoplasia.

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may systemically induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins by penetrating the gut epithelial barrier. Once in the blood stream, these pro-inflammatory mediators activate immune cells, which release pro-inflammatory molecules, many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes/Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including lupus nephritis, MPO-ANCA vasculitis, and Goodpasture's syndrome. Therapies that enhance SCFA-producing bacteria in the gut have powerful therapeutic potential. Dietary fiber is fermented by gut bacteria which in turn release SCFAs that protect the gut barrier, as well as modulating immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs.

The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8.

The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively).

Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.

An expanding corpus of research robustly substantiates the complex interrelation between gut microbiota and the onset, progression, and metastasis of colorectal cancer. Investigations in both animal models and human subjects have consistently underscored the role of gut bacteria in a variety of metabolic activities, driven by dietary intake. These activities include amino acid metabolism, carbohydrate fermentation, and the generation and regulation of bile acids. These metabolic derivatives, in turn, have been identified as significant contributors to the progression of colorectal cancer. This thorough review meticulously explores the dynamic interaction between gut bacteria and metabolites derived from the breakdown of amino acids, fatty acid metabolism, and bile acid synthesis. Notably, bile acids have been recognized for their potential carcinogenic properties, which may expedite tumor development. Extensive research has revealed a reciprocal influence of gut microbiota on the intricate spectrum of colorectal cancer pathologies. Furthermore, strategies to modulate gut microbiota, such as dietary modifications or probiotic supplementation, may offer promising avenues for both the prevention and adjunctive treatment of colorectal cancer. Nevertheless, additional research is imperative to corroborate these findings and enhance our comprehension of the underlying mechanisms in colorectal cancer development.

Polysaccharides are commonly used as low-toxicity anticancer active substances to enhance the chemotherapeutic effect of cisplatin and reduce toxicity. Brassica rapa L. polysaccharides have been shown to have hepatoprotective effects; however, their anticancer effects in combination with cisplatin and their mechanisms have not been reported. An acidic polysaccharide from Brassica rapa L. (BRCPe) using hydroalcohol precipitation-assisted sonication was Characterized. The effects of BRCPe combined with cisplatin treatment on tumor growth in hepatocellular carcinoma mouse model were investigated. The impact of the combined treatment on the composition of intestinal flora, levels of short-chain fatty acids and endogenous metabolites in tumor mice were analyzed based on macrogenomic and metabolomic data Our results showed that the BRCPe combined with low-dose Cisplatin group showed better inhibitory activity against hepatocellular carcinoma cell growth in terms of tumor volume, tumor weight, and tumor suppression rate compared with the BRCPe and Cisplation alone group, and reduced the side effects of cisplatin-induced body weight loss, immune deficiency, and liver injury. Furthermore, BRCPe combined with cisplatin was found to induce apoptosis in hepatocellular carcinoma cell through the activation of the caspase cascade reaction. In addition, the intervention of BRCPe were observed to modulate the composition, structure and functional structure of intestinal flora affected by cisplatin. Notably, Lachnospiraceae bacteria, Lactobacillus murinus, Muribaculaceae, and Clostridiales bacteria were identified as significant contributors to microbial species involved in metabolic pathways. Moreover, BRCPe effectively regulate the metabolic disorders in cisplatin-induced hepatocellular carcinoma mice. In conclusion, BRCPe could potentially function as an adjuvant or dietary supplement to augment the effectiveness of cisplatin chemotherapy through the preservation of a more efficient intestinal microenvironmental homeostasis.

Short chain fatty acids (SCFAs) produced by gut microbiota are known to play primary roles in gut homeostasis by immunomodulation partially through G-protein coupled receptors (GPR) 43. Using mouse models of TLR ligand induced keratitis, we investigated whether SCFAs and GPR43 play any regulatory roles in the pathogenesis of inflammatory responses in the eye.

Both human and mouse eyes were labeled with a specific antibody for GPR43 and imaged by a laser scanning confocal microscope. Corneal cups from naïve C57BL/6J (B6) and GPR43 knockout (KO) mice were stimulated with TLR ligands in the presence or absence of sodium butyrate overnight and then processed for RT-PCR assay for expression of GPR43 and cytokines. Keratitis was induced by Poly I:C in wild type (WT) B6, GPR43KO and chimeric mice and the disease severity was evaluated by the corneal fluorescein staining test, and infiltrating cell staining and calculating in corneal whole mount.

GPR43 is expressed in both human and mouse eyes and the expression is bidirectionally regulated by TLR ligands and butyrate. Butyrate significantly inhibited inflammation caused by several TLR ligands such as Poly I:C, Flagellin, and CpG-ODN (TLR-3, 5 and 9 agonists, respectively) in WT, but not GPR43KO, mice. Butyrate inhibition of TLR-induced keratitis is mediated by the GPR43 expressed in tissue but not hematopoietic, cells.

This is the first report to demonstrate of the protective effect of SCFAs on microbial keratitis, and the dynamic expression and anti-inflammatory function of GPR43 in the eye. SCFAs can modulate inflammation and immunity in the eye through GPR43.

Patients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19.

We conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants.

Twenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants (p = 0.07). Linear discriminant analysis revealed differences in the abundance of short-chain fatty acid-producing gut microbiota for each SARS-CoV-2 variant. Fecal metabolome analysis showed that the Omicron and Delta variants had markedly reduced propionic and lactic acid levels compared to the Alpha strain (p < 0.05).

The intestinal microbiota of patients with COVID-19 varies depending on the SARS-CoV-2 variant. Dysbiosis of the intestinal microbiota due to differences in SARS-CoV-2 variants causes a decrease in intestinal short-chain fatty acids.