Western diets are linked to metabolic disorders such as Type 2 diabetes mellitus (T2DM) and diabetic dyslipidemia, which involve hyperglycemia, insulin resistance, high plasma cholesterol levels and altered lipoprotein profiles. The T2DM progression also involves glucolipotoxicity, wherein elevated glucose and fatty acid levels induce oxidative stress and inflammation. Excessive intake of saturated fats and/or cholesterol can trigger dysbiosis, which weakens the colonic barrier, increases its permeability, and promotes chronic low-grade inflammation, thereby accelerating the progression of T2DM. Silicon, an essential trace element, has demonstrated antidiabetic, hypolipidemic, antioxidant and anti-inflammatory properties, suggesting its potential as a nutritional adjuvant in therapeutic management of T2DM and the maintenance of gut health. In this study, 24 male Wistar rats were divided into three groups: (1) an early-stage T2DM group (ED) fed a control meat incorporated into a high saturated-fat diet; (2) a late-stage T2DM group (LD) fed a control meat incorporated into a high-saturated fat and high cholesterol diet combined with streptozotocin and nicotinamide injection; and (3) a late-stage T2DM group fed a silicon enriched meat (LD-Si). Microbiota composition, lipoperoxidation and concentrations of fat, cholesterol, oxysterols and short-chain fatty acids and silicon were assayed in feces. The colonic tissue morphology, barrier integrity, antioxidant capacity and inflammatory markers were measured to evaluate the impact of silicon on colonic health and intestinal barrier function. Silicon enriched meat (Si-RM) consumption increased faecal fat and cholesterol excretion and reduced toxic luminal environments by modulating oxysterols. Si-RM consumption also enhanced colonic barrier integrity, increasing tight junction proteins and goblet cells, and exhibited antioxidant effects via the pNrf2 pathway and superoxide dismutase activity. Furthermore, silicon reduced the pro-inflammatory cytokines TNFα and IL-6, likely through inhibition of the TLR4/NFκB pathway. The results suggest that silicon's ability to enhance intestinal barrier integrity, reduce oxidative stress, and prevent inflammation could slow down T2DM progression, making it a promising nutritional adjuvant for managing the disease.

Environmental factors can play fundamental role in health in childhood and adulthood during critical developmental periods like lactation. The maternal intake of probiotics like kefir during lactation could benefit newborns' intestinal health. This study aimed to evaluate the effects of maternal kefir intake during lactation on bacterial breast milk composition and the gut microbiota of offspring Wistar male rats at weaning. Lactating Wistar rats and their pups were divided into four groups based on litter size and maternal kefir intake. Sequencing of the 16S rRNA gene in breast milk revealed the predominance of the Proteobacteria, Firmicutes, and Actinobacteriota phyla. Offspring gut microbiota exhibited clustering tendencies in kefir groups with varying genus abundance. Additionally, maternal kefir intake led to increased levels of butyrate acid in offspring faeces (> +30%, p > 0.05). These findings show that the lactation period could be a window of opportunity to program intestinal health through microbiota modulation.

Aerobic exercise exerts a significant impact on the gut microbiota imbalance and atherosclerosis induced by a high-fat diet. However, whether fecal microbiota transplantation, based on aerobic exercise, can improve atherosclerosis progression remains unexplored. In this study, we utilized male C57 mice to establish models of aerobic exercise and atherosclerosis, followed by fecal microbiota transplantation(Fig 1a). Firstly, we analyzed the body weight, somatotype, adipocyte area, and aortic HE images of the model mice. Our findings revealed that high-fat diet -induced atherosclerosis mice exhibited elevated lipid accumulation, larger adipocyte area, and more severe atherosclerosis progression. Additionally, we assessed plasma lipid levels, inflammatory factors, and gut microbiota composition in each group of mice. high-fat diet -induced atherosclerosis mice displayed dyslipidemia along with inflammatory responses and reduced gut microbiota diversity as well as abundance of beneficial bacteria. Subsequently performing fecal microbiota transplantation demonstrated that high-fat diet -induced atherosclerosis mice experienced weight loss accompanied by reduced lipid accumulation while normalizing their gut microbiota profile; furthermore it significantly improved blood lipids and inflammation markers thereby exhibiting notable anti- atherosclerosis effects. The findings suggest that aerobic exercise can modify gut microbiota composition and improve high-fat diet-induced atherosclerosis(Fig 1b). Moreover, these beneficial effects can be effectively transmitted through fecal microbiota transplantation, offering a promising therapeutic approach for managing atherosclerosis.

Although low-dose lactulose has shown a good theoretical foundation for the treatment of ulcerative colitis (UC) in previous studies, the exact effects and mechanism remain unclear. The rats were randomly distributed into 5 groups, i.e., normal drinking water was provided for an initial 14 days in blank control group, 4% dextran sulfate sodium was used for modeling in the remaining 4 groups. During the 15-24th day, rats in the blank control group were administered with 0.9% saline (0.5 ml/d) by gavage. In the rest 4 groups, rats were administered 0.9% saline (0.5 ml/d, UC model), mesalazine (400 mg/kg/d), lactulose (1000 mg/kg/d), and lactulose + mesalazine (two-drug combination) by gavage. In addition to symptoms and pathological changes, serum IL-6, TNF-α, and High-sensitivity C-reactive protein(Hs-CRP) by ELISA analysis, mRNA and protein expression levels of TLR-2, TLR-4, Nuclear factor-κB(NF-κB), IL-6, and TNF-α in colon tissues by RT-qPCR and WB analyses respectively. Meanwhile, short-chain fatty acid(SCFAs) and intestinal flora were analyzed. Low-dose lactulose improved symptoms (diarrhea, blood in stool, weight loss) and pathological inflammation. In addition to serum IL-6, TNF-α, and Hs-CRP, the mRNA and protein expression levels of TLR-2, TLR-4, NF-κB, IL-6 and TNF-α in the colon were down-regulated with the intervention of lactulose.Meanwhile, lactulose decreased the ileocecal PH, increased SCFAs and altered the intestinal flora. Low-dose lactulose may be beneficial to UC by regulating TLRs/NF-κB pathway, reducing ileocecal PH, increasing SCFAs, regulating intestinal flora and improving the intestinal mucosal barrier. Meanwhile, low-dose lactulose and mesalazine may have additive effects upon combination.

Silicon (Si), a newer trace element, is believed to be important for healthy bone formation and to decrease bone resorption, improving the quality of bone by manipulating several hormones and enzymes. Therefore, the current investigation was conducted to determine the impact of Si supplementation on growth, immunity, antioxidant, hormonal profile and biomarkers of bone health in pre-ruminant crossbred calves. Twenty-four crossbred calves (5-7 days) were selected on the basis of their body weight (BW 31.65 ± 0.46 kg) and divided into 4 groups (n = 6) and fed as per ICAR (2013) feeding standards except that these were additionally supplemented with 0 (Si0), 50 (Si50), 100 (Si100) and 150 (Si150) mg of Si/kg dry matter (DM) in four respective groups for 90 days. Every month, peripheral blood samples were drawn (0, 30, 60 and 90 days post supplementing with Si) and analysed for antioxidant status, hormonal profile and bone health biomarkers. It is reported that dietary Si supplementation improved (P < 0.05) net body weight gain (kg), average daily gain (g) and average dry matter intake (kg), whereas feed intake (kg/100 kg BW), was not altered due to Si supplementation. Structural growth measurements were significantly higher (P < 0.05) in Si100 and Si150 groups as compared to Si50 and control groups. However, immune response (humoral as well as cell-mediated immunity), erythrocytic antioxidant enzymes (superoxide dismutase, SOD, glutathione peroxidase, GPx and catalase), plasma ferric reducing total antioxidant power (FRAP) activity and the plasma concentration of total immunoglobulins (TIg) remained unaffected by Si supplementation. Silicon increased (P < 0.05) the concentration of plasma growth hormone (GH), vitamin D3, bone alkaline phosphatase (BALP) and osteocalcin (OCN) in Si100 and Si150 groups, but the levels of calcitonin, parathyroid hormone (PTH) and hydroxyproline (HYP) remained similar among all the groups. As a result of the current investigation, it can be inferred that the inclusion of 100 and 150 mg of Si/kg DM was effective in improving the growth performance, growth hormone, vitamin D3 and bone health status in pre-ruminant calves. However, supplementation of 150 mg of Si/kg DM had no additional benefit; therefore 100 mg of Si/kg DM is the optimum level of Si supplementation in pre-ruminant calves.

Drinking water is an essential daily intake to hydrate the body. It is conceivable that water, when endowed with antioxidant properties, will be the most natural radical terminator surpassing conventional pill-based or food-derived antioxidants. However, current end-of-pipe purification of municipal water generally depletes minerals pivotal for antioxidant potency. To surmount this dilemma, we assemble a multistage and multifunctional water treatment system using various filter materials that dislodge contaminants, mineralize water and impart reductive attributes. The mineralized reduced water (MRW) generated by this system possesses an ideal antioxidant water quality with weak alkalinity, negative oxidation-reduction potential and rich minerals including calcium, magnesium, zinc and silicon. This water decreases oxidative products in vivo via counteracting reactive oxygen species and activating the endogenous antioxidant system governed by nuclear factor erythroid 2-related factor 2. Moreover, long-term intake of MRW effectively retards xenografted tumor growth without any discernible hematologic and organic toxicity. These findings portend enormous promise for MRW in the prevention and treatment of oxidative stress-related maladies and even antiaging.

Ulva lactuca, a green seaweed, may be an alternative source of nutrients and bioactive compounds for weaned piglets. However, it has a recalcitrant cell wall rich in a sulphated polysaccharide - ulvan - that is indigestible to monogastrics. The objective of this study was to evaluate the effect of dietary incorporation of 7% U. lactuca, combined with carbohydrases supplementation (commercial carbohydrase mixture or recombinant ulvan lyase), on growth performance, nutrient digestibility and gut health parameters (morphology and microbiota) of weaned piglets. The experiment was conducted over 14 days using 40 weaned piglets randomly allocated to one of four experimental diets: a control diet based on wheat-maize-soybean meal, a diet with 7% U. lactuca replacing the control diet (UL), a diet with UL supplemented with 0.005% Rovabio® Excel AP, and a diet with UL supplemented with 0.01% of a recombinant ulvan lyase. The dietary treatments had no major effects on growth performance, nitrogen balance and gut content variables, as well as histological measurements. Contrarily, dry matter and organic matter digestibility decreased with dietary seaweed inclusion, while hemicellulose digestibility increased, suggesting a high fermentability of this cell wall fraction independently of carbohydrases supplementation. Some beneficial microbial populations increased as a consequence of enzymatic supplementation (e.g., Prevotella), while seaweed diets as a whole led to an increased abundance of Shuttleworthia, Anaeroplasma and Lachnospiraceae_NK3A20_group, all related with a healthier gut. It also decreased Lactobacillus when compared to controls, which is possibly related to increased bioavailability of seaweed zinc. This study indicates that, under these experimental conditions, up to 7% dietary U. lactuca has no detrimental effect on piglet growth, despite decreasing acid detergent fibre digestibility. Carbohydrases supplementation of Ulva diets is not required at this incorporation level.

Human exposure to heavy metals, which encompasses both essential and toxic varieties, is widespread. The intestine functions as a critical organ for absorption and metabolism of heavy metals. Gut microbiota plays a crucial role in heavy metal absorption, metabolism, and related processes. Toxic heavy metals (THMs), such as arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd), can cause damage to multiple organs even at low levels of exposure, and it is crucial to emphasize their potential high toxicity. Nevertheless, certain essential trace elements, including iron (Fe), copper (Cu), and manganese (Mn), play vital roles in the biochemical and physiological functions of organisms at low concentrations but can exert toxic effects on the gut microbiota at higher levels. Some potentially essential micronutrients, such as chromium (Cr), silicon (Si), and nickel (Ni), which were considered to be intermediate in terms of their essentiality and toxicity, had different effects on the gut microbiota and their metabolites. Bidirectional relationships between heavy metals and gut microbiota have been found. Heavy metal exposure disrupts gut microbiota and influences its metabolism and physiological functions, potentially contributing to metabolic and other disorders. Furthermore, gut microbiota influences the absorption and metabolism of heavy metals by serving as a physical barrier against heavy metal absorption and modulating the pH, oxidative balance, and concentrations of detoxification enzymes or proteins involved in heavy metal metabolism. The interactions between heavy metals and gut microbiota might be positive or negative according to different valence states, concentrations, and forms of the same heavy metal. This paper reviews the metabolic interactions of 10 common heavy metals with the gut microbiota and their health implications. This collated information could provide novel insights into the disruption of the intestinal microbiota caused by heavy metals as a potential contributing factor to human diseases.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine N-oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, P < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, P = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, P = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, P < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, P < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, P = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event.NEW & NOTEWORTHY The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).

Microbiomes that can serve as an indicator of gut, intestinal, and general health of humans and animals are largely influenced by food consumed and contaminant bioagents. Microbiome studies usually focus on estimating the alpha (within sample) and beta (similarity/dissimilarity among samples) diversities. This study took a combinatorial approach and applied machine learning to microbiome data to predict the presence of disease-causing pathogens and their association with known/potential probiotic taxa. Probiotics are beneficial living microorganisms capable of improving the host organism's digestive system, immune function and ultimately overall health. Here, 16 S rRNA gene high-throughput Illumina sequencing of temporal pre-harvest (feces, soil) samples of 42 pastured poultry flocks (poultry in this entire work solely refers to chickens) from southeastern U.S. farms was used to generate the relative abundance of operational taxonomic units (OTUs) as machine learning input. Unique genera from the OTUs were used as predictors of the prevalence of foodborne pathogens (Salmonella, Campylobacter and Listeria) at different stages of poultry growth (START (2-4 weeks old), MID (5-7 weeks old), END (8-11 weeks old)), association with farm management practices and physicochemical properties.

While we did not see any significant associations between known probiotics and Salmonella or Listeria, we observed significant negative correlations between known probiotics (Bacillus and Clostridium) and Campylobacter at the mid-time point of sample collection. Our data indicates a negative correlation between potential probiotics and Campylobacter at both early and end-time points of sample collection. Furthermore, our model prediction shows that changes in farm operations such as how often the houses are moved on the pasture, age at which chickens are introduced to the pasture, diet composition and presence of other animals on the farm could favorably increase the abundance and activity of probiotics that could reduce Campylobacter prevalence.

Integration of microbiome data with farm management practices using machine learning provided insights on how to reduce Campylobacter prevalence and transmission along the farm-to-fork continuum. Altering management practices to support proliferation of beneficial probiotics to reduce pathogen prevalence identified here could constitute a complementary method to the existing but ineffective interventions such as vaccination and bacteriophage cocktails usage. Study findings also corroborate the presence of bacterial genera such as Caloramator, DA101, Parabacteroides and Faecalibacterium as potential probiotics.

Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we investigate the effect of a delactosed buffalo milk whey by-product (DMW) on colorectal carcinogenesis.

The effect of DMW on colorectal carcinoma (CRC) was investigated in the established mouse model of azoxymethane (AOM)-induced colon carcinoma, which closely resembles the human clinical condition of CRC. The effect of DMW on CRC immortalized cell lines was also evaluated to further identify the antineoplastic mechanism of action.

Pretreatment of AOM-treated mice with DMW significantly (P < 0.05) reduced the percentage of mice bearing both aberrant crypt foci with more than four crypts (which are early precancerous lesions that progress to CRC) and tumors. In addition, DMW completely counteracted the effect of AOM on protein expression of caspase-9, cleaved caspase-3 and poly ADP-ribose polymerase in colonic tissue. Administration of DMW alone (i.e. without AOM) resulted in changes in the composition of the gut microbiota, leading to enrichment or depletion of genera associated with health and disease, respectively. DMW was also able to restore AOM-induced changes in specific genera of the gut microbiota. Specifically, DMW reduced the genera Atopobiaceae, Ruminococcus 1 and Lachnospiraceae XPB1014 and increased the genera Parabacteroides and Candidatus Saccharimonas, which were increased and reduced, respectively, by AOM. Blood levels of butyric acid and cancer diagnostic markers (5-methylcytidine and glycerophosphocholine), which were increased by AOM treatment, were reduced by DMW. Furthermore, DMW exerted cytotoxic effects on two human CRC cell lines (HCT116 and HT29) and these effects were associated with the induction of apoptotic signaling.

Our results suggest that DMW exerts chemopreventive effects and restores the gut microbiota in AOM-induced CRC, and induces cytotoxic effect on CRC cells. DMW could be an important dietary supplement to support a healthy gut microbiota and reduce the prevalence of CRC in humans. Video Abstract.

Lactobacillus acidophilus (LA) and Astragalus polysaccharides (APS) have each been shown to have anti-osteoporotic activity, and the aim of this study was to further investigate whether the LA fermenting APS was more effective in improving calcium absorption and osteoporosis than the unfermented mixed solution (MS). We found that the fermentation solution (FS) intervention improved the calcium absorption, BMD, and bone microarchitecture in osteoporotic rats and resulted in better inhibition of osteoclast differentiation markers ACP-5 and pro-inflammatory cytokines TNF-α and IL-6 and promotion of osteoblast differentiation marker OCN. This better performance may be due to the improved restoration of the relative abundance of specific bacteria associated with improved calcium absorption and osteoporosis such as Lactobacillus, Allobaculum, and UCG-005. Several key metabolites, including indicaxanthin, chlorogenic acid, and 3-hydroxymelatonin, may also be the key to the better improvement. In conclusion, the LA fermenting APS can better improve calcium absorption and osteoporosis by increasing active metabolites and altering gut microbiota. This finding should become a solid foundation for the development of LA fermenting APS in functional foods.

Dendrobium officinale is a traditional Chinese medicine for treating gastrointestinal diseases by nourishing "Yin" and thickening the stomach lining. To study whether D. officinale endophytes can colonize the intestinal tract and regulate gut microbiota in mice, we used autoclave steam sterilizing and 60Co-γ radiation to eliminate D. officinale endophytes from its juice. Then, high-throughput ITS1-ITS2 rDNA and 16S rRNA gene amplicons were sequenced to analyze the microbial community of D. officinale endophytes and fecal samples of mice after administration of fresh D. officinale juice. Sterilization of D. officinale juice by autoclaving for 40 min (ASDO40) could more effectively eliminate the D. officinale endophytes and decrease their interference on the gut microbiota. D. officinale juice could increase beneficial gut microbiota and metabolites including short-chain fatty acids. D. officinale endophytes Pseudomonas mosselii, Trichocladium asperum, Titata maxilliformis, Clonostachys epichloe, and Rhodotorula babjevae could colonize the intestinal tract of mice and modulate gut microbiota after oral administration of the juice for 28 days. Thus, the regulatory effect of D. officinale juice on gut microbiota was observed, which provides a basis for inferring that D. officinale endophytes might colonize the intestinal tract and participate in regulating gut microbiota to treat diseases. Thus, this study further provides a new approach for the treatment of diseases by colonizing plant endophytes in the intestinal tract and regulating gut microbiota.

This study evaluated the potential effects of adding acidifiers to the drinking water on the growth performance, complete blood count, antioxidant indicators, and diversity of gastrointestinal microbiota for weaned pigs. A total of 400 weaned pigs were randomly divided into four treatments. Pigs were fed the same basal diet and given either water (no acidifier was added, control) or water plus blends of different formulas of acidifiers (acidifier A1, A2, or A3) for 35 days. On d 18 and 35 of the experimental period, 64 pigs (four pigs per pen) were randomly selected to collect blood for a CBC test (n = 128) and an antioxidant indicators test (n = 128); 24 pigs (six pigs per group) were randomly selected to collect fresh feces (n = 48) from the rectum for 16S rRNA gene sequencing. Compared to the control, supplementing the drinking water with acidifiers improved the growth performance and survival rate of weaned pigs. Acidifier groups also increased serum catalase (CAT) and total antioxidant capacity (T-AOC) activities, while also displaying a decreased malondialdehyde (MDA) concentration compared to the control. The relative abundance of Firmicutes in the acidifier A1 group was greater than that in the control group (p < 0.05) on d 35; the relative abundance of Lactobacillus in the acidifier A1 group was greater than that in the control group (p < 0.05) on d 18 and 35. The microbial species Subdoligranulum or Ruminococcaceae_UCG-005 had significantly positive correlations with ADG and ADFI or with serum antioxidant indicators, respectively. These findings suggest that supplementing the drinking water with an acidifier has a potential as an antioxidant, which was reflected in the improvement of growth performance, immunity, antioxidant capacity, and intestinal flora.