Production Of Short-chain Fatty Acids Research Articles

Changes in short-chain fatty acids affect brain development in mice with early life antibiotic-induced dysbacteriosis.

Early enteral nutrition and the gut microbiota profoundly influence neonatal brain development, with short-chain fatty acids (SCFAs) from the microbiota playing a pivotal role. Understanding the relationship between dysbiosis, SCFAs, and brain development is crucial. In this study, we investigated the impact of antibiotics on the concentration of SCFAs in neonatal feces. Additionally, we developed a model of gut dysbiosis in neonatal mice to examine the potential relationship between this imbalance, SCFAs production, and brain function development. We measured the SCFAs content in the feces of two groups of neonates, categorized based on whether antibiotics were used, and conducted the Neonatal Behavioral Neurological Assessment (NBNA) test on all neonates. Then we evaluated fecal SCFAs levels in neonates and neonatal mice post-antibiotic treatment using liquid chromatography-mass spectrometry (LC-MS) analysis. Morris water maze (MWM) tests assessed behavioral performance, and western blot analysis examined brain tissue-related proteins-neuron-specific enolase (NSE), ionized calcium binding adaptor molecule-1 (IBA1), and myelin basic proteins (MBP). The use of antibiotics did not affect the NBNA scores of the two groups of neonates, but it did reduce the SCFAs content in their feces. Antibiotic administration induced gut dysbiosis in mice, resulting in decreased IBA1 and MBP expression. Interventions to restore gut microbiota ameliorated these effects. Mice with dysbiosis displayed cognitive deficits in the MWM test. SCFAs levels decreased during dysbiosis, and increased upon microbiota recovery. Neonatal dysbiosis affects the microbiota-gut-brain axis, impairing cognitive function and nervous system development. Reduced SCFAs may contribute significantly to these alterations.

Salinomycin, a potent inhibitor of XOD and URAT1, ameliorates hyperuricemic nephropathy by activating NRF2, modulating the gut microbiota, and promoting SCFA production

Long-term hyperuricemia can induce kidney damage, clinically referred to as hyperuricemic nephropathy (HN), which is characterized by renal fibrosis, inflammation, and oxidative stress. However, currently used uric acid-lowering drugs are not capable of protecting the kidneys from damage. Therefore, uric acid-lowering drugs that can also protect the kidneys are urgently needed. In this study, we first discovered that salinomycin, an antibiotic, can regulate uric acid homeostasis and ameliorate kidney damage in mice with HN. Mechanistically, salinomycin inhibited serum and hepatic xanthine oxidase (XOD) activities and downregulated renal urate transporter 1 (URAT1) expression and transport activity, thus exerting uric acid-lowering effects in mice with HN. Furthermore, we found that salinomycin promoted p-NRF2 Ser40 expression, resulting in increased nuclear translocation of NRF2 and activation of NRF2. More importantly, salinomycin affected the gut microbiota and promoted the generation of short-chain fatty acids (SCFAs) in mice with HN. In conclusion, our results revealed that salinomycin maintains uric acid homeostasis and alleviates kidney injury in mice with HN by multiple mechanisms, suggesting that salinomycin might be a desirable candidate for HN treatment in the clinic.

Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice.

Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated. The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT. Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry.

Combination of magnetite and sodium percarbonate to enhance acetate-enriched short-chain fatty acids production during sludge anaerobic fermentation

Large amounts of waste activated sludge are generated daily worldwide, posing significant environmental challenges. Anaerobic fermentation is a promising method for sludge disposal, but it has two technical bottlenecks: the availability of short-chain fatty acids (SCFAs)-producing substrates and SCFAs consumption by methanogenesis. This study proposes a pretreatment strategy combining sodium percarbonate (SPC) and magnetite (Fe3O4) to address these issues. Under optimized conditions (20 mg Fe3O4/g TSS and 15 mg SPC/g TSS), SCFAs production increased to 3244.10 ± 216.31 mg COD/L, about 3.06 times the control (1057.29 ± 35.06 mg COD/L) and surpassing reported treatments. The combined pretreatment enhanced the disruption of extracellular polymeric substances, increased the release of biodegradable matters, improved acidogenesis enzyme activities, and inhibited methanogenesis. Additionally, it increased NH4+-N release in favor of the recovery of phosphorus from sludge residual. This study demonstrates an efficient pretreatment for high SCFAs production and resource recovery from WAS.

Insight into response mechanism of short-chain fatty acids to refined microbial transformation order of dissolved organic matter ranked by molecular weight during dry anaerobic digestion

Dynamic transformation of dissolved organic matter (DOM) contributes to short-chain fatty acids (SCFAs) production during anaerobic digestion. However, the impact of refined transformation of DOM ranked by molecular weight (MW) on SCFAs has never been investigated. Results indicated that DOM conversion order was 3500–7000 Da>(MW>14000 Da) > 7000–4000 Da during hydrolysis stage, while it was independent of their MW in acidogenesis phase and followed a low to high MW order during methanogenesis stage. Proteins-like DOMs with different MW were closely related to SCFAs. Eight groups of microorganisms (e.g., Bacillus and Caldicoprobacter) responsible for the conversion of proteins-like DOMs to SCFAs. The possible routes linking environmental properties to microorganisms-proteins-like DOMs-SCFAs connections were constructed. Microbial activity modifications by regulating moisture, pH, NO3−-N and NH4+-N can expedite the conversion of proteins-like DOMs to SCFAs. The study emphasizes the importance of MW-classification-based biotransformation of organic waste, offering a potential strategy to enhance anaerobic digestion performance.

RG-I pectic polysaccharides and hesperidin synergistically modulate gut microbiota: An in vitro study targeting the proportional relationship

In this study, we investigated how different proportions blends of Rhamnogalacturonan-I pectic polysaccharides and hesperidin impact the gut microbiota and metabolites using an in vitro simulated digestion and fermentation model. The results indicated that both of them could modulate the gut microbiota and produce beneficial metabolites. However, their blends in particular proportions (such as 1:1) exhibited remarkable synergistic effects on modulating the intestinal microenvironment, surpassing the effects observed with individual components. Specifically, these blends could benefit the host by increasing short-chain fatty acids production (such as acetate), improving hesperidin bioavailability, producing more metabolites (such as hesperetin, phenolic acids), and promoting the growth of beneficial bacteria. This synergistic and additive effect was inseparable from the role of gut microbiota. Certain beneficial bacteria, such as Blautia, Faecalibacterium, and Prevotella, exhibited strong preferences for those blends, thereby contributing to host health through participating in carbohydrate and flavonoid metabolism.

Effects of 1-oleate-2-palmitate-3-linoleate glycerol supplementation on the small intestinal development and gut microbial composition of neonatal mice

Recent studies have shown that 1-oleo-2-palmito-3-linoleyl glycerol (OPL) is the most abundant triacylglycerol in human breast milk in China. Epidemiologic studies have shown that sn-2 palmitate improves the absorption of fatty acids and calcium in infants. However, there have been few studies of the specific mechanism by which OPL affects intestinal function. In the present study, we have characterized the effects of various levels of OPL supplementation on the development of the intestinal epithelium and the intestinal microbiota of neonatal mice. OPL supplementation increased the body masses and intestinal lengths of weaned mice and promoted defecation. These positive effects were related to the effect of OPL to promote the development of intestinal villi and crypts. OPL increased the expression of the intestinal stem cell markers Olfm4 and Sox9 in the jejunum and ileum, which promoted their differentiation into goblet cells and Paneth cells. It also promoted the integrity of the epithelial barrier by increasing the secretion of mucin 2 and lysozyme 1 and the expression of the tight junction proteins occludin, ZO1, claudin 2, and claudin 3. More importantly, we found that low dose-OPL promotes the transformation of the intestinal microbiota of neonatal mice to the mature state in 3-month-old mice, increases the proportion of Firmicutes, and reduces the proportion of Bacteroidota. The proportions of anaerobic genera of bacteria, such as Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ligilactobacillus, and Bifidobacterium were higher, as were the key producers of short-chain fatty acids, such as Bacteroides and Blautia. OPL also increased the butyric acid content of the feces, which significantly correlated with the abundance of Lactobacillus. High-dose OPL tended to be more effective at promoting defecation and the development of the villi and crypts, but these effects did not significantly differ from those achieved using the lower dose. A low dose of OPL was more effective at increasing the butyric acid content and causing the maturation of microbes. In summary, the OPL supplementation of newborn mice promotes the establishment of the intestinal epithelial layer structure and barrier function, and also promotes the transformation of the intestinal microbiota to a mature state. This study lays a theoretical foundation for the inclusion of OPL in infant formula and provides a scientific basis for the development of intestinal health products.

L-Theanine Alleviates Ulcerative Colitis by Regulating Colon Immunity via the Gut Microbiota in an MHC-II-Dependent Manner.

Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.

Different Short-Chain Fatty Acids Unequally Modulate Intestinal Homeostasis and Reverse Obesity-Related Symptoms in Lead-Exposed High-Fat Diet Mice.

Our previous study showed that heavy metal lead (Pb) exposure exacerbates high-fat-diet (HFD)-induced metabolic damage and significantly depletes the gut microbiota-derived metabolite short-chain fatty acid (SCFA) levels. However, it remains unclear whether SCFA is a key metabolite involved in accelerating adverse consequences after Pb exposure. In this study, we explored the effects of exogenous supplementation of acetate, propionate, and butyrate on a metabolic disorder model in Pb-exposed HFD mice. We found that three SCFA interventions attenuated glycolipid metabolism disorders and liver damage, with butyrate performing the best effects in improving obesity-related symptoms. All three SCFA promoted the abundance of Muribaculaceae and Muribaculum, acetate specifically enriched Christensenellaceae, Blautia, and Ruminococcus, and butyrate specifically enriched Parasutterella, Rikenella, Prevotellaceae_UCG-001, and Bacteroides, which contributed to the positive promotion of SCFA production forming a virtuous cycle. Besides, butyrate inhibited Gram-negative bacteria Escherichia-Shigella. All of these events alleviated the intestinal Th17/Treg imbalance and inflammatory response through crosstalk between the G protein-coupled receptor (GPR)/histone deacetylase 3 (HDAC3) and lipopolysaccharide (LPS)/toll-like receptors 4 (TLR4)/nuclear factor κ-B (NF-κB) pathways and ultimately improved the intestinal barrier function. SCFA further upregulated the monocarboxylate transporter 1 (MCT1) and GPR43/adenosine 5'-monophosphate-activated protein kinase (AMPK) pathways to inhibit hepatic lipid accumulation. Overall, SCFA, especially butyrate, is an effective modulator to improve metabolic disorders in obese individuals exposed to heavy metals by targeting gut microecology.

Food-breastmilk combinations alter the colonic microbiome of weaning infants: an in silico study.

The introduction of solid foods to infants, also known as weaning, is a critical point for the development of the complex microbial community inhabiting the human colon, impacting host physiology in infancy and later in life. This research investigated in silico the impact of food-breastmilk combinations on growth and metabolite production by colonic microbes of New Zealand weaning infants using the metagenome-scale metabolic model named Microbial Community. Eighty-nine foods were individually combined with breastmilk, and the 12 combinations with the strongest influence on the microbial production of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were identified. Fiber-rich and polyphenol-rich foods, like pumpkin and blackcurrant, resulted in the greatest increase in predicted fluxes of total SCFAs and individual fluxes of propionate and acetate when combined, respectively, with breastmilk. Identified foods were further combined with other foods and breastmilk, resulting in 66 multiple food-breastmilk combinations. These combinations altered in silico the impact of individual foods on the microbial production of SCFAs and BCFAs, suggesting that the interaction between the dietary compounds composing a meal is the key factor influencing colonic microbes. Blackcurrant combined with other foods and breastmilk promoted the greatest increase in the production of acetate and total SCFAs, while pork combined with other foods and breastmilk decreased the production of total BCFAs.IMPORTANCELittle is known about the influence of complementary foods on the colonic microbiome of weaning infants. Traditional in vitro and in vivo microbiome methods are limited by their resource-consuming concerns. Modeling approaches represent a promising complementary tool to provide insights into the behavior of microbial communities. This study evaluated how foods combined with other foods and human milk affect the production of short-chain fatty acids and branched-chain fatty acids by colonic microbes of weaning infants using a rapid and inexpensive in silico approach. Foods and food combinations identified here are candidates for future experimental investigations, helping to fill a crucial knowledge gap in infant nutrition.

Deer oil improves ulcerative colitis induced by DSS in mice by regulating the intestinal microbiota and SCFAs metabolism and modulating NF-κB and Nrf2 signaling pathways.

Deer oil (DO), a byproduct of deer meat processing, possesses high nutritional value. This study aims to evaluate the protective effects of DO on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and to explore its potential mechanisms of action. DO was found to inhibit weight loss and colon shortening in colitis mice, significantly reduce disease activity index scores, and notably enhance the levels of tight junction proteins in colon tissues, thus improving intestinal barrier function. ELISA results indicated that DO markedly alleviated the mice's oxidative stress and inflammatory responses. Western blot analysis further demonstrated that DO significantly inhibited the phosphorylation of NF-κB while up-regulating the expression levels of Nrf2 and HO-1 proteins. Additionally, DO increased the abundance of beneficial bacteria such as Odoribacter, Blautia, and Muribaculum, reduced the abundance of harmful bacteria such as Bacteroides, Helicobacter, and Escherichia-Shigella, and promoted the production of short-chain fatty acids. Our study provides the first evidence that DO can effectively improve DSS-induced UC in mice. The underlying mechanisms may involve maintaining intestinal barrier function, inhibiting inflammation, alleviating oxidative stress, and modulation of gut microbiota. These findings offer valuable insights for developing DO as an adjunct treatment for UC and as a functional food. © 2024 Society of Chemical Industry.

Developing a novel hypothesis to enhance mental resilience via targeting Faecalibacterium prausnitzii in gut-brain axis

Social stress (SS) can lead to mental disorders (MD) in some people, such as depression and anxiety, while others who are resilient can handle SS without showing signs of mental illness. Resilience is characterized by human capacity to adapt to life’s adverse events without losing function or developing a mental disorder. Exploring molecular processes can help elucidate resilience mechanisms that counteract the pathophysiology of depression. Gut microbiome plays an essential role in the homeostasis of human body, especially the central nervous system (CNS). Therefore, it may support the counterbalance of certain disorders, such as depression, through the microbiota-gut-brain (MGB) axis. Short-chain fatty acids (SCFAs) produced by the gut microbiota, such as butyrate, increase the transmission activity of neurotransmitters, brain-derived neurotrophic factor (BDNF) expression and the regulation of microglia maturation enhances resilience in response to stress. Probiotics can be engineered to yield more butyrate. However, the overproduction of SCFAs is not necessarily beneficial and may lead to known side effects, such as intestinal dysbiosis or metabolic dysfunction. Herein, as we hypothesized the potential effect of the microbiome in resilience promotion, we have designed a cortisol-sensitive operon that allows gut microbiota to regulate the production of SCFAs according to the environmental demands which produces butyrate only when responding to stress. Amongst gut bacteria, Faecalibacterium prausnitzii (F. prausnitzii) has large amounts of butyrate and can be manipulated by designed plasmid, a process which makes it a suitable candidate to be translated into clinic.

Isoorientin Alleviates DSS-Treated Acute Colitis in Mice by Regulating Intestinal Epithelial P-Glycoprotein (P-gp) Expression.

Isoorientin (ISO) is a naturally occurring flavonoid with diverse functional properties that mitigate the risk of diseases stemming from oxidation, inflammation, and cancer cell proliferation. P-glycoprotein (P-gp) is a vital component of the intestinal epithelium and may play a role in the onset of intestinal inflammatory conditions, such as inflammatory bowel disease (IBD). Recent studies have suggested that short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) produced by the gut microbiota stimulate the increase of P-gp expression, alleviating excessive inflammation and thereby preservation of intestinal homeostasis. ISO has been shown to improve colon health and modulate the gut microbiota. In this study, we aimed to explore whether ISO can modulate the microbes and their metabolites to influence P-gp expression to alleviate IBD. First, the impact of ISO on dextran sulfate sodium (DSS)-treated colitis in mice was investigated. Second, 16S rRNA gene sequencing was conducted. The present study indicated that ISO mitigated the symptoms and pathological damage associated with DSS-treated colitis in mice. Western blot analysis revealed ISO upregulated P-gp in colon tissues, suggesting the critical role of P-gp protein in intestinal epithelial cells. 16S microbial diversity sequencing revealed ISO restored the richness and variety of intestinal microorganisms in colitis-bearing mice and enriched SCFA-producing bacteria, such as Lachnospiraceae_NK4A136_group. The experiments also revealed that the ISO fecal microbiota transplantation (FMT) inoculation of DSS-treated mice had similarly beneficial results. FMT mice showed a reduction in colitis symptoms, which was more pronounced in ISO-FMT than in CON-FMT mice. Meanwhile, ISO-FMT expanded the abundance of beneficial microorganisms, increased the expression of metabolites, such as SCFAs and total SBAs, and significantly upregulated the expression of P-gp protein. In addition, Spearman's correlation analysis demonstrated a positive correlation between the production of SCFAs and SBAs and the expression of P-gp. The present study identified that ISO increases the expression of P-gp in the intestinal epithelium by regulating intestinal microorganisms and their metabolites, which maintains colonic homeostasis, improves the integrity of the colonic epithelium, and alleviates colitis.

Combining the Vaginal Microbiome and Serum Metabolome to Screen for Potential Biomarkers of Early Pregnancy in Cows.

Early pregnancy diagnostic techniques are of significant importance in livestock farming, particularly in dairy farming. This study aimed to screen artificially inseminated cows for potential biomarkers at day 21 of pregnancy using microbiota-metabolomics analysis. The microbiome analysis revealed significant changes (p < 0.05) in the composition and abundance of the vaginal microbiota in cows after pregnancy. Notably, there was an increase in the abundance of [Eubacterium]_hallii_group (p < 0.05) associated with the production of short-chain fatty acids in the pregnant group compared with the non-pregnant group. Furthermore, significant alterations were observed in the serum metabolome, with notable changes in the concentrations of prolyl-hydroxyproline (Pro-Hyp) (p < 0.01) and bonactin (p < 0.01). The majority of differential metabolites clustered within the pathways of amino acid metabolism and lipid metabolism, with lipid metabolism exhibiting a higher proportion and playing a pivotal role in early pregnancy. An enzyme-linked immunosorbent assay was employed to quantify three key metabolites of the arachidonic acid pathway. The results demonstrated significant decreases in serum concentrations of leukotriene B4 (LTB4) (p < 0.05) and prostaglandin F2α (PGF2α) (p < 0.01) and no significant changes in arachidonic acid (AA) (NS) concentrations after 21 days of gestation in cows. Spearman's correlation analysis was utilized to investigate the interrelationship between the vaginal microbiota and serum metabolites. In conclusion, the present study demonstrated that biomaterials such as bonactin, Pro-hyp, LTB4, PGF2α in serum metabolites and [Eubacterium]_hallii_group in the vaginal flora of cows could be utilized as potential biomarkers for 21 days of gestation in cows.

Genomic Face-Off: An In Silico Comparison of the Probiotic Potential of Lactobacillus spp. and Akkermansia muciniphila

Introduction: The gut microbiota plays a crucial role in maintaining human health, and probiotics have gained significant attention for their potential benefits. Among the diverse array of gut bacteria, Akkermansia muciniphila, and Lactobacillus spp. have emerged as promising candidates for their putative probiotic properties. Method: In this study, we conducted a comprehensive comparative in silico analysis of the genomes of A. muciniphila and Lactobacillus to decipher their probiotic potential. Utilizing a range of bioinformatics tools, we evaluated various genomic attributes, including functional gene content, metabolic pathways, antimicrobial peptide production, adhesion factors, and stress response elements. These findings revealed distinctive genomic signatures between the two genera. A. muciniphila genomes exhibited a high prevalence of mucin-degrading enzymes, suggesting a specialized adaptation for mucin utilization in the gut environment. Results: Additionally, the presence of specific pathways for short-chain fatty acid production highlighted its potential impact on host health. Lactobacillus genomes, on the other hand, demonstrated a diverse repertoire of functional genes associated with probiotic attributes, including the production of antimicrobial peptides and adhesion factors, indicating potential for host-microbe interactions and immune modulation. Furthermore, this analysis unveiled the genetic basis of stress tolerance in both genera, revealing conserved mechanisms for surviving the dynamic conditions of the gut ecosystem. Conclusion: This study also shed light on the distribution of antibiotic-resistance genes, allowing us to assess safety concerns associated with their potential use as probiotics. Overall, this comparative in silico exploration provides valuable insights into the genomic foundation of A. muciniphila and Lactobacillus probiotic potential. These findings contribute to the understanding of their respective roles within the gut microbiota and offer a foundation for further experimental investigations. As probiotic applications continue to expand, this study advances our knowledge of the genetic underpinnings that govern their functionality and highlights promising avenues for future therapeutic interventions and personalized health strategies.

Early and late gut microbiota signatures of stroke in high salt-fed stroke-prone spontaneously hypertensive rats

The high salt-fed stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable tool to study the mechanisms underlying stroke pathogenesis. Salt intake modifies the gut microbiota (GM) in rats and humans and alterations of the GM have previously been associated with increased stroke occurrence. We aimed to characterize the GM profile in SHRSPs fed a high-salt stroke-permissive diet (Japanese diet, JD), compared to the closely related stroke-resistant control (SHRSR), to identify possible changes associated with stroke occurrence. SHRSPs and SHRSRs were fed a regular diet or JD for 4 weeks (short-term, ST) or a maximum of 10 weeks (long-term, LT). Stroke occurred in SHRSPs on JD-LT, preceded by proteinuria and diarrhoea. The GM of JD-fed SHRSPs underwent early and late compositional changes compared to SHRSRs. An overrepresentation of Streptococcaceae and an underrepresentation of Lachnospiraceae were observed in SHRSPs JD-ST, while in SHRSPs JD-LT short-chain fatty acid producers, e.g. Lachnobacterium and Faecalibacterium, decreased and pathobionts such as Coriobacteriaceae and Desulfovibrio increased. Occludin gene expression behaved differently in SHRSPs and SHRSRs. Calprotectin levels were unchanged. In conclusion, the altered GM in JD-fed SHRSPs may be detrimental to gut homeostasis and contribute to stroke occurrence.

Yeast β-glucan alleviates high-fat diet-induced Alzheimer's disease-like pathologies in rats via the gut-brain axis

Targeting the gut microbiota may be an emerging strategy for the prevention and treatment of Alzheimer's disease (AD). Macro-molecular yeast β-glucan (BG), derived from the yeast of Saccharomyces cerevisiae, regulates the gut microbiota. This study aimed to investigate the effect and mechanism of long-term BG in high-fat diet (HFD)-induced AD-like pathologies from the perspective of the gut microbiota. Here, we found that 80 weeks of BG treatment ameliorated HFD-induced cognitive dysfunction in rats. In the hippocampus, BG alleviated HFD-induced the activation of astrocytes, microglia, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome pathway, and AD-like pathologies. BG modulated gut dysbiosis through increasing the levels of beneficial bacteria and short-chain fatty acids (SCFAs). BG also attenuated HFD-induced gut barrier impairment. Correlation analysis revealed a close relationship among microbiota, SCFAs, and AD-like pathologies. Furthermore, the fecal microbiota of BG-treated rats and SCFAs treatment mitigated AD-like pathologies via the NLRP3 inflammasome pathway in HFD-fed aged rats. These results suggested that long-term BG promotes the production of SCFAs derived from gut microbiota, which further inhibits NLRP3 inflammasome-mediated neuroinflammation, thereby alleviating HFD-induced AD-like pathologies in rats. BG may become a new strategy for targeting neurodegenerative diseases.

Interactions between soluble dietary fibers from three edible fungi and gut microbiota

Edible fungi are emerging as a valuable dietary fiber source with health benefits, where their bioactivity hinges on their structure. This study targets the structure-activity relationship of soluble dietary fibers from Lentinus edodes (LESDF), Agaricus bisporus (ABSDF), and Hericium erinaceus (HESDF), focusing on their impact on gut microbiota and health. We explored the properties and structures of edible fungi, finding their soluble fibers affect metabolites and gut microbiota by increasing gas and lowering pH. Among these, HESDF demonstrated superior effects (pH: △1.4 ± 0.07; Gas production: △24.5 ± 0.4 mL). Furthermore, different types of edible fungi dietary fiber exhibited distinct capabilities in promoting the production of short-chain fatty acids by gut microorganisms. For instance, ABSDF exceled in acetic acid production (26.12 ± 0.35 mM) and propionic acid production (9.50 ± 0.13 mM), while HESDF stood out in butyric acid production (17.86 ± 0.09 mM). LESDF showed higher levels of Phascolarctobacterium, ABSDF had elevated levels of Ruminococcus, and HESDF displayed increased levels of Faecalibacterium. These results contribute to our understanding of how soluble dietary fiber from different edible fungi impacts gut microbiota and offers insights for the development and utilization of these fibers as functional food.

Inulin Supplementation Alleviates Ochratoxin A-Induced Kidney Injury through Modulating Intestinal Microbiota.

Ochratoxin A (OTA) is a prevalent mycotoxin found in feed that causes significant kidney injury in animals. Further investigation was needed to devise strategies for treating OTA-induced kidney damage through the gut-kidney axis. Evidence indicates the crucial role of intestinal microbiota in kidney damage development. Inulin, a dietary fiber, protects kidneys by modulating intestinal microbiota and promoting short-chain fatty acid (SCFA) production. However, its precise mechanism in OTA-induced kidney damage remained unclear. In this study, chickens were orally administered OTA and inulin for 2 weeks to investigate inulin's effects on OTA-induced kidney damage and underlying mechanisms. The alteration of intestinal microbiota, SCFAs contents, and SCFA receptors was further analyzed. Results demonstrated that inulin supplementation influenced intestinal microbiota, increased SCFAs production, and mitigated OTA-induced kidney damage in chickens. The importance of microbiota in mediating inulin's renal protection was further confirmed by antibiotic and fecal microbiota transplantation experiments. Additionally, inulin exhibited antioxidant and anti-inflammatory properties, alleviating NLRP3 inflammasome activation and pyroptosis. In summary, inulin protected chickens from OTA-induced kidney damage, which might provide a potential strategy to mitigate the harmful effects of mycotoxins through prebiotics and safeguard renal health.

Dietary nitrate maintains intestinal epithelia homeostasis in aged mice.

The intestinal tract, which is the primary site of digestion and absorption of nutrients, is one of the most vulnerable organs during aging. Dietary nitrate, which is mainly derived from the diet and absorbed in the intestinal tract, is a key messenger that connecting oral and general health. However, whether dietary nitrate regulates intestinal tract homeostasis remains unclear. Our data revealed that the serum and salivary nitrate levels decreased during mice aging. The functional proteins of the epithelial barrier (E-cadherin, Claudin-1 and Zonula Occludens-1) in the colon tissues decreased during the aging process. Long-term nitrate supplement in drinking water restored the serum and salivary nitrate levels and increased the functional proteins expression of the colon epithelial barrier. Dietary nitrates increase the relative abundance of some intestinal probiotics, particularly those associated with the production of short-chain fatty acids, such as Blautia, Alloprevotella, Butyricicoccus, and Ruminococcaceae, while promoting the butyric acid production in the colon. Moreover, the expression of Sialin (encoded by Slc17a5), which is a nitrate transporter, increased in the colon epithelial cells by nitrate supplementation. The epithelial cell-conditional Slc17a5-knockout mutant mice (K14-cre; Slc17a5fl/fl) revealed that the functional proteins expression of the colon epithelial barrier and the proliferation of PCNA-positive intestinal epithelial cells in the colon crypts was significantly decreased compared with those of the K14-cre; Slc17a5fl/+ mice. Taken together, our findings suggested that nitrate supplementations were associated with the increased expression of colonic epithelial barriers-related proteins and the increased Sialin expression. Nitrate may serve as a potential therapeutic approach in maintaining aged colonic homeostasis.