Metabolites Short-chain Fatty Acids Research Articles

Protective effect and mechanism insight of purified Antarctic krill phospholipids against mice ulcerative colitis combined with bioinformatics

Antarctic krill oil is functional oil and has a complex phospholipids composition that poses difficulties in elucidating its effect mechanism on ulcerative colitis (UC). The mechanism of UC action was studied by bioinformatics, and the therapeutic effect of Antarctic krill phospholipids (APL) on dextran sulfate sodium (DSS)-induced colitis mice was verified. GO functional enrichment analysis uncovered an enrichment of these genes in the regulation of cell–cell adhesion, membrane region, signaling receptor activator activity, and cytokine activity. Meanwhile, the KEGG results revealed the genes were enriched in the TNF signaling pathway, pathogenic Escherichia coli infection, inflammatory bowel disease and tight junction. Animal experiments showed that APL treatment alleviated the UC symptoms and reduced inflammatory damage. Meanwhile, the expressions of the tight junction (TJ) proteins, ZO-1 and occludin, were restored, and the levels of IL-6 and TNF-α were reduced. Moreover, Firmicutes/Bacteroidetes ratio in the intestinal microbiota was regulated, and the contents of short-chain fatty acids metabolites were raised. These findings would provide an insight for the beneficial effects of APL and dietary therapy strategies for UC.

The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy.

Intestinal microbiota homeostasis and the gut-brain axis are key players associated with host health and alterations in metabolic, inflammatory, and neurodegenerative disorders. Sepsis-associated encephalopathy (SAE), which is closely associated with bacterial translocation, is a common secondary organ dysfunction and an urgent, unsolved problem affecting patient quality of life. Our study examined the neuroprotective effects of the gut microbiome and short-chain fatty acid (SCFA) metabolites on SAE. Male C57BL/6 mice were administered SCFAs in drinking water, then subjected to cecal ligation and puncture (CLP) surgery to induce SAE. 16S rRNA sequencing was used to investigate gut microbiome changes. The open field test (OFT) and Y-maze were performed to evaluate brain function. The permeability of the blood-brain barrier (BBB) was assessed by Evans blue (EB) staining. Hematoxylin and eosin (HE) staining was used to examine intestinal tissue morphology. The expression levels of tight junction (TJ) proteins and inflammatory cytokines was assessed by western blots and immunohistochemistry. In vitro, bEND.3 cells were incubated with SCFAs and then with lipopolysaccharide (LPS). Immunofluorescence was used to examine the expression of TJ proteins. The composition of the gut microbiota was altered in SAE mice; this change may be related to SCFA metabolism. SCFA treatment significantly alleviated behavioral dysfunction and neuroinflammation in SAE mice. SCFAs upregulated occludin and ZO-1 expression in the intestine and brain in SAE mice and LPS-treated cerebromicrovascular cells. These findings suggested that disturbances in the gut microbiota and SCFA metabolites play key roles in SAE. SCFA supplementation could exert neuroprotective effects against SAE by preserving BBB integrity.

Breast milk jaundice affects breastfeeding: From the perspective of intestinal flora and SCFAs-GPR41/43.

Breast milk jaundice (BMJ) is one of the main factors leading to interruption or early termination of breastfeeding. Interrupting breastfeeding to treat BMJ may increase the adverse consequences for infant growth and disease prevention. The Intestinal flora and metabolites are increasingly recognized as a potential therapeutic target in BMJ. First, dysbacteriosis can lead to a decrease in the metabolite short-chain fatty acids. At the same time, SCFA can act on specific G protein-coupled receptors 41 and 43 (GPR41/43), and a decrease in SCFA downregulates the GPR41/43 pathway, leading to a diminished inhibition of intestinal inflammation. In addition, intestinal inflammation leads to a decrease in intestinal motility and a large amount of bilirubin enters the enterohepatic circulation. Ultimately, these changes will result in the development of BMJ. In this review, we will describe the underlying pathogenetic mechanism of the intestinal flora effects on BMJ.

Therapeutic Potential of Gut Microbiota and Its Metabolite Short-Chain Fatty Acids in Neonatal Necrotizing Enterocolitis

Short chain fatty acids (SCFAs), the principle end-products produced by the anaerobic gut microbial fermentation of complex carbohydrates (CHO) in the colon perform beneficial roles in metabolic health. Butyrate, acetate and propionate are the main SCFA metabolites, which maintain gut homeostasis and host immune responses, enhance gut barrier integrity and reduce gut inflammation via a range of epigenetic modifications in DNA/histone methylation underlying these effects. The infant gut microbiota composition is characterized by higher abundances of SCFA-producing bacteria. A large number of in vitro/vivo studies have demonstrated the therapeutic implications of SCFA-producing bacteria in infant inflammatory diseases, such as obesity and asthma, but the application of gut microbiota and its metabolite SCFAs to necrotizing enterocolitis (NEC), an acute inflammatory necrosis of the distal small intestine/colon affecting premature newborns, is scarce. Indeed, the beneficial health effects attributed to SCFAs and SCFA-producing bacteria in neonatal NEC are still to be understood. Thus, this literature review aims to summarize the available evidence on the therapeutic potential of gut microbiota and its metabolite SCFAs in neonatal NEC using the PubMed/MEDLINE database.

Effects of radon exposure on gut microbiota and its metabolites short-chain fatty acids in mice

Radon (222Rn) is a naturally occurring radioactive gas. Forty percent of the natural radiation to which the human body is exposed comes from radon gas. Long-term exposure to high concentrations of radon induces systemic damage. However, the effect of such exposure on gut microbiota still remains unclear. We explored the effects of radon exposure on gut microbiota and its metabolites short-chain fatty acids (SCFAs) in BALB/c mice by cumulative inhalation of radon at 30, 60, and 120 working level months (WLM). The radon-exposed mice showed slow body weight gain, decreased serum triglycerides and low-density lipoproteins, decreased diversity, lower community structure, and altered abundance of the gut microbiota. Lachnospiraceae, Amaricoccus, and Enterococcus could differentiate the IR30, 60, and 120 WLM groups, respectively. Meanwhile, radon exposure affected the metabolic functions of the gut microbiota, mainly carbohydrate, amino acid, and lipid metabolic pathways. The altered abundance of microbiota and resulting reduced levels of SCFAs may aggravate the damage caused by radon exposure.

Effects of prebiotics on intestinal physiology, neuropsychological function, and exercise capacity of mice with sleep deprivation

People suffered from insufficient or disrupted sleep due to night shifts, work pressure, and irregular lifestyles. Sleep deprivation caused by inadequate quantity or quality of sleep has been associated with not only increased risk of metabolic diseases, gut dysbiosis, and emotional disorders but also decreased work and exercise performance. In this study, we used the modified multiple platform method (MMPM) to induce pathological and psychological characteristics of sleep deprivation with C57BL/6J male mice, and investigated whether supplementing a prebiotics mixture of short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) (9:1 ratio) could improve the impacts of sleep deprivation on intestinal physiology, neuropsychological function, inflammation, circadian rhythm, and exercise capacity. Results showed that sleep deprivation caused intestinal inflammation (increased TNFA and IL1B) and decreased intestinal permeability with a significant decrease in the tight junction genes (OCLN, CLDN1, TJP1, and TJP2) of intestine and brain. The prebiotics significantly increased the content of metabolite short-chain fatty acids (acetate and butyrate) while recovering the expression of indicated tight junction genes. In hypothalamus and hippocampus, clock (BMAL1 and CLOCK) and tight junction (OCLN and TJP2) genes were improved by prebiotics, and corticotropin-releasing hormone receptor genes, CRF1 and CRF2, were also significantly regulated for mitigation of depression and anxiety caused by sleep deprivation. Also, prebiotics brought significant benefits on blood sugar homeostasis and improvement of exercise performance. Functional prebiotics could improve physiological modulation, neuropsychological behaviors, and exercise performance caused by sleep deprivation, possibly through regulation of inflammation and circadian rhythm for health maintenance. However, the microbiota affected by prebiotics and sleep deprivation should warrant further investigation.

Characterization of Short-chain fatty acid-producing and cholesterol assimilation potential probiotic Lactic acid bacteria from Chinese fermented rice

Probiotic strains are phrased as beneficial for life because this bacterial association has substantial effects on human and animal health when administrated orally, among which bio-active metabolite short-chain fatty acids production and cholesterol assimilation are most significant. All the short-chain fatty acids, mainly acetate, propionate, and butyrate reveal valuable effects on human health. In this research, the ability of 9 the potential lactic acid bacteria food-isolated probiotics was investigated to produce bio-active metabolite short-chain fatty acids directly or indirectly, and cholesterol-lowering ability through various mechanisms. Their 16S rRNA gene sequences were analyzed. short-chain fatty acids were quantified by gas chromatography, while cholesterol assimilation was measured using the o-phthalaldehyde method with slight modifications. All isolated strains through this study have the ability to optimize cholesterol content in the culture broth, short-chain fatty acid production, and survival in extreme alkaline and acidic conditions. The highest resistance to bile salt concentrations, γ-hemolysis, and strong antibacterial activity against pathogenic indicators, especially Escherichia coliATCC25922. The highest Lipid accumulation inhibitory effect was noticed in Lentilactobacillus hilgardii LMG 07934 as a potential probiotic isolate on the basis of cholesterol assimilation capacity (i.e., 91.4%), along with the ability to produce abundant i.e., butyric acid, propionic acid, and acetic acid, followed by Lacticaseibacillus paracasei ATCC 334 which has 85.3% cholesterol assimilation ability. These findings demonstrated that these isolated strains from Chinese fermented rice can be used as a potential probiotic and alternate therapeutic supplement because of their ability to produce short-chain fatty acids and their cholesterol-lowering ability.

Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy.

Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota-immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids. We also comprehensively delineate how disruption in the microbiota-immune axis results in immune-mediated diseases, such as gastrointestinal infections, inflammatory bowel diseases, cardiometabolic disorders (e.g., cardiovascular diseases, diabetes, and hypertension), autoimmunity (e.g., rheumatoid arthritis), hypersensitivity (e.g., asthma and allergies), psychological disorders (e.g., anxiety), and cancer (e.g., colorectal and hepatic). We further encompass the role of fecal microbiota transplantation, probiotics, prebiotics, and dietary polyphenols in reshaping the gut microbiota and their therapeutic potential. Continuing, we examine how the gut microbiota modulates immune therapies, including immune checkpoint inhibitors, JAK inhibitors, and anti-TNF therapies. We lastly mention the current challenges in metagenomics, germ-free models, and microbiota recapitulation to a achieve fundamental understanding for how gut microbiota regulates immunity. Altogether, this review proposes improving immunotherapy efficacy from the perspective of microbiome-targeted interventions.

Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion.

Clear roles and mechanisms in explaining gut microbial dysbiosis and microbial metabolites short-chain fatty acids (SCFAs) alterations in chronic cerebral ischemic pathogenesis have yet to be explored. In this study, we investigated chronic cerebral hypoperfusion (CCH)-induced gut microbiota and metabolic profiles of SCFAs as well as the effects and mechanisms of fecal microbiota transplantation (FMT) and SCFAs treatment on CCH-induced hippocampal neuronal injury. Bilateral common carotid artery occlusion (BCCAo) was used to establish the CCH model. Gut microbiota and SCFAs profiles in feces and hippocampus were evaluated by 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. RNA sequencing analysis was performed in hippocampal tissues. The potential molecular pathways and differential genes were verified through western blot, immunoprecipitation, immunofluorescence, and ELISA. Cognitive function was assessed via the Morris water maze test. Ultrastructures of mitochondria and synapses were tested through a transmission electron microscope. Chronic cerebral hypoperfusion induced decreased fecal acetic and propionic acid and reduced hippocampal acetic acid, which were reversed after FMT and SCFAs administration by changing fecal microbial community structure and compositions. Furthermore, in the hippocampus, FMT and SCFAs replenishment exerted anti-neuroinflammatory effects through inhibiting microglial and astrocytic activation as well as switching microglial phenotype from M1 toward M2. Moreover, FMT and SCFAs treatment alleviated neuronal loss and microglia-mediated synaptic loss and maintained the normal process of synaptic vesicle fusion and release, resulting in the improvement of synaptic plasticity. In addition, FMT and SCFAs supplement prevented oxidative phosphorylation dysfunction via mitochondrial metabolic reprogramming. The above effects of FMT and SCFAs treatment led to the inhibition of CCH-induced cognitive impairment. Our findings highlight FMT and SCFAs replenishment would be the feasible gut microbiota-based strategy to mitigate chronic cerebral ischemia-induced neuronal injury.

Research progress of Eubacterium and its metabolite short-chain fatty acids in regulating type 2 diabetes mellitus

Intestinal flora and its metabolites are closely related to the progression of type 2 diabetes mellitus(T2DM). Eubacterium is one of the dominant intestinal flora, and its metabolites short-chain fatty acids (SCFAs) play a leading role in regulating intestinal metabolic balance. It has been reported that SCFAs can regulate the secretion of glucagon-like peptide-1, improve the function of pancreatic β cells, participate in bile acids metabolism and regulate the production of inflammatory factors in T2DM. Based on the above research background, this article mainly reviews the relationship between Eubacterium and its metabolite SCFAs and T2DM and its regulatory mechanism.

Fecal microbiota transplantation and replenishment of short-chain fatty acids protect against chronic cerebral hypoperfusion-induced colonic dysfunction by regulating gut microbiota, differentiation of Th17 cells, and mitochondrial energy metabolism

BackgroundLittle is known about the association between gut microbiota and intestinal injury under a state of chronic cerebral hypoperfusion (CCH). Here, the effects of gut microbiota and short-chain fatty acids (SCFAs), as important metabolic products, on intestinal function and potential mechanisms after CCH were investigated.MethodsRats were subjected to bilateral common carotid artery occlusion (BCCAo) to induce CCH. The gut microbiota and metabolites of SCFAs were assessed by 16S rRNA sequencing and targeted metabolomics, respectively. Transcriptomic analysis of colon tissues was also conducted. Subsequently, potential molecular pathways and differentially expressed genes were verified by western blot, immunoprecipitation, and immunofluorescence analyses. Furthermore, the integrity of the colonic barrier was evaluated by hematoxylin and eosin and mucin 2 staining and expression levels of tight junction proteins. Besides, colonic inflammation was further assessed by flow cytometry and expression levels of inflammatory cytokines. In addition, colonic mitochondrial dysfunction was analyzed via membrane potential, reactive oxygen species, electron transport chain (ETC) activities, adenosine triphosphate content, and mitochondrial ultrastructure.ResultsCCH modified gut microbial composition and microbial metabolism of SCFAs, which may be associated with inhibition of mitochondrial ETC activities and oxidative phosphorylation, leading to dysregulation of mitochondrial energy metabolism. Furthermore, CCH induced differentiation of pathogenic Th17 cells, promoted the formation of complexes of interferon regulatory factor 4 and signal transducer and activator of transcription 3 (STAT3), and increased the phosphorylation of STAT3. This was associated with an impairment of colonic barrier function and chronic colonic inflammation. In contrast, FMT and SCFA replenishment ameliorated CCH-induced gut microbial dysbiosis by increasing the intestinal content of Ruminococcus_sp_N15_MGS_57 and modulating microbial metabolism of SCFAs by increasing acetic acid contents associated with an improvment of the balance between Tregs and Th17 cells, mitochondrial ETC activities, and oxidative phosphorylation to prevent colonic inflammation and dysregulation of mitochondrial energy metabolism.ConclusionThese findings indicate that FMT and SCFA replenishment present a promising therapeutic strategy against colonic dysfunction under a state of chronic cerebral ischemia.

Folic Acid Protects against Hyperuricemia in C57BL/6J Mice via Ameliorating Gut-Kidney Axis Dysfunction.

Emerging lines of research evidence point to a vital role of gut-kidney axis in the development of hyperuricemia (HUA), which has been identified as an increasing burden worldwide due to the high prevalence. The involved crosstalk which links the metabolic and immune-related pathways is mainly responsible for maintaining the axial homeostasis of uric acid (UA) metabolism. Nowadays, the urate-lowering drugs only aim to treat acute gouty arthritis as a result of their controversial clinical application in HUA. In this study, we established the HUA model of C57BL/6J mice to evaluate the effectiveness of folic acid on UA metabolism and further explored the underlying mechanisms. Folic acid attenuated the kidney tissue injury and excretion dysfunction, as well as the typical fibrosis in HUA mice. Molecular docking results also revealed the structure-activity relationship of the folic acid metabolic unit and the UA transporters GLUT9 and URAT1, implying the potential interaction. Also, folic acid alleviated HUA-induced Th17/Treg imbalance and intestinal tissue damage and inhibited the active state of the TLR4/NF-κB signaling pathway, which is closely associated with the circulating LPS level caused by the impaired intestinal permeability. Furthermore, the changes of intestinal microecology induced by HUA were restored by folic acid, including the alteration in the structure and species composition of the gut microbiome community, and metabolite short-chain fatty acids. Collectively, this study revealed that folic acid intervention exerted improving effects on HUA by ameliorating gut-kidney axis dysfunction.

Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets

Intestinal oxidative stress triggers gut microbiota dysbiosis, which is involved in the etiology of post-weaning diarrhea and enteric infections. Ellagic acid (EA) can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota dysbiosis. Therefore, we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage, oxidative stress, and dysbiosis of gut microbiota in weanling piglets. A total of 126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2mL saline orally (Ctrl group), or the basal diet supplemented with 0.1% EA and 2mL saline orally (EA group), or the basal diet and 2mL fecal microbiota suspension from the EA group orally (FEA group), respectively, for 14d. Compared with the Ctrl group, EA group improved growth performance by increasing average daily feed intake and average daily weight gain (P<0.05) and decreasing fecal scores (P<0.05). EA group also alleviated intestinal damage by increasing the tight junction protein occludin (P<0.05), villus height, and villus height-to-crypt depth ratio (P<0.05), while decreasing intestinal epithelial apoptosis (P<0.05). Additionally, EA group enhanced the jejunum antioxidant capacity by increasing the total antioxidant capacity (P<0.01), catalase (P<0.05), and glutathione/oxidized glutathione (P<0.05), but decreased the oxidative metabolite malondialdehyde (P<0.05) compared to the Ctrl group. Compared with the Ctrl group, EA and FEA groups increased alpha diversity (P<0.05), enriched beneficial bacteria (Ruminococcaceae and Clostridium ramosum), and increased metabolites short-chain fatty acids (P<0.05). Correspondingly, FEA group gained effects comparable to those of EA group on growth performance, intestinal damage, and intestinal antioxidant capacity. In addition, the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices (P<0.05). Overall, dietary EA supplementation could improve growth performance and attenuate intestinal damage and oxidative stress by regulating the gut microbiota in weanling piglets.

A sensitive and accurate GC–MS method for analyzing microbial metabolites short chain fatty acids and their hydroxylated derivatives in newborn fecal samples

Short chain fatty acids (SCFAs), crucial intestinal bacterial metabolites, have been widely accepted as potential diagnostic markers in neonatal medicine. Nevertheless, it is still a great challenge to accurately quantify SCFAs in newborn fecal samples due to the huge variation of water content, limited commercial isotope-labeled internal standards and poor sensitivity. In this study, Na2CO3 solution (50 μg/mL) was applied to convert the free SCFAs to SCFA sodium salts, which could prevent the loss of violate SCFAs during lyophilization process. Furthermore, N-methylbenzylamine-d0/d3 was applied as the chemical derivatization regent to enhance the sensitivity and accuracy. Based on this method, the SCFA contents in meconium and neonatal fecal samples were analyzed to illustrate the change of SCFAs during the gut microbiome development. Chemical derivatization based on N-methylbenzylamine-d0/d3 could not only significantly promote the sensitivity (323–1280 folds compared to free SCFAs) by promoting the ionization efficiency, but also provide one-to-one isotope internal standards. Moreover, 7 SCFAs, including acetic acid (2), n-butyric acid (4), isobutyric acid (5), 2-hydroxybutyric acid (11), 2-hydroxy-3-methylbutyric acid (13), 3-hydroxybutyric acid (14), 2-hydroxy-2-methylbutyric acid (17) were found to be significantly increased in neonatal fecal samples compared to the meconium fecal samples. All these results proved that this method could be applied for SCFA analysis in newborn fecal samples with perfect accuracy and sensitivity.

Connecting gut microbiomes and short chain fatty acids with the serotonergic system and behavior in Gallus gallus and other avian species.

The chicken gastrointestinal tract has a diverse microbial community. There is increasing evidence for how this gut microbiome affects specific molecular pathways and the overall physiology, nervous system and behavior of the chicken host organism due to a growing number of studies investigating conditions such as host diet, antibiotics, probiotics, and germ-free and germ-reduced models. Systems-level investigations have revealed a network of microbiome-related interactions between the gut and state of health and behavior in chickens and other animals. While some microbial symbionts are crucial for maintaining stability and normal host physiology, there can also be dysbiosis, disruptions to nutrient flow, and other outcomes of dysregulation and disease. Likewise, alteration of the gut microbiome is found for chickens exhibiting differences in feather pecking (FP) behavior and this alteration is suspected to be responsible for behavioral change. In chickens and other organisms, serotonin is a chief neuromodulator that links gut microbes to the host brain as microbes modulate the serotonin secreted by the host's own intestinal enterochromaffin cells which can stimulate the central nervous system via the vagus nerve. A substantial part of the serotonergic network is conserved across birds and mammals. Broader investigations of multiple species and subsequent cross-comparisons may help to explore general functionality of this ancient system and its increasingly apparent central role in the gut-brain axis of vertebrates. Dysfunctional behavioral phenotypes from the serotonergic system moreover occur in both birds and mammals with, for example, FP in chickens and depression in humans. Recent studies of the intestine as a major site of serotonin synthesis have been identifying routes by which gut microbial metabolites regulate the chicken serotonergic system. This review in particular highlights the influence of gut microbial metabolite short chain fatty acids (SCFAs) on the serotonergic system. The role of SCFAs in physiological and brain disorders may be considerable because of their ability to cross intestinal as well as the blood-brain barriers, leading to influences on the serotonergic system via binding to receptors and epigenetic modulations. Examinations of these mechanisms may translate into a more general understanding of serotonergic system development within chickens and other avians.

Insoluble Fiber in Barley Leaf Attenuates Hyperuricemic Nephropathy by Modulating Gut Microbiota and Short-Chain Fatty Acids

Hyperuricemia (HUA), characterized by abnormal serum uric acid (UA) levels, is recognized as an important risk factor for hyperuricemic nephropathy (HN), which is strongly linked to gut microbiota. This study investigated the protective effects and regulatory mechanisms of insoluble fiber from barley leaves (BL) against HN, induced by adenine (Ad) and potassium oxonate (PO). The results showed that BL dramatically reduced the levels of serum UA and creatinine (CR) and alleviated renal injury and fibrosis. Moreover, BL modulated oxidative stress and downregulated the expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidneys of mice with HN. In addition, the 16S rRNA sequence data showed that BL also increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria, including Bacteroides, Alloprevotella, and Eisenbergiella. Besides, BL treatment also increased SCFAs levels. Of interest, the application of SCFAs in hyperuricemic mice effectively reduced their serum UA. Furthermore, SCFAs dose-dependently inhibited URAT1 and GLUT9 in vitro and potently interacted with URAT1 and GLUT9 in the docking analysis. When taken together, our results indicate that BL and its metabolite SCFAs may be potential candidates for relieving HUA or HN.

Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation.

Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites&lt;sup&gt;1,2&lt;/sup&gt;, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. The effects of inulin are microbiota dependent and were reproduced in mice colonized with human-derived microbiota. Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. Finally, we demonstrate that inulin enhances allergen- and helminth-induced type 2 inflammation. Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence.

The Role of Short Chain Fatty Acids in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by abdominal pain and disordered bowel habits. The etiology of IBS is multifactorial, including abnormal gut-brain interactions, visceral hypersensitivity, altered colon motility, and psychological factors. Recent studies have shown that the intestinal microbiota and its metabolites short chain fatty acids (SCFAs) may be involved in the pathogenesis of IBS. SCFAs play an important role in the pathophysiology of IBS. We discuss the underlying mechanisms of action of SCFAs in intestinal inflammation and immunity, intestinal barrier integrity, motility, and the microbiota-gut-brain axis. Limited to previous studies, further studies are required to investigate the mechanisms of action of SCFAs in IBS and provide more precise therapeutic strategies for IBS.

Analysis of the effect of phototherapy on intestinal probiotics and metabolism in newborns with jaundice.

BackgroundIn clinical practice, oral probiotics are often given to children with hyperbilirubinaemia who receive phototherapy, but the exact mechanism of the action of the probiotics on hyperbilirubinaemia remains unclear. It is unclear how the effects of phototherapy on the probiotic flora in the neonatal gut, in particular.Materials and methodsFifty newborns who needed phototherapy from June 2018 to June 2020 were selected as the study subjects, and five healthy newborns in the same period were used as controls to analyse the changes in probiotic bacteria in their faeces.Results1. In the intestinal tracts of newborns, Bifidobacterium is the main probiotic strain, with a small amount of Lactobacillus. There were probiotic species changes in the neonatal intestinal microbiota after phototherapy for 24 and 48 h. The amount of Bifidobacterium and Lactobacillus decreased significantly (P < 0.05). 2. A correlation analysis of probiotic species and bile acid metabolism indexes showed that Bifidobacterium was positively correlated with many metabolites (P < 0.05), such as chenodeoxycholic acid, hyodeoxycholic acid, cholic acid, allocholic acid, and β-cholic acid. It was also negatively correlated with many metabolites (P < 0.05), such as glycocholic acid, sodium, sodium tudca, and chenodeoxycholic acid. Lactobacillus was negatively correlated with metabolites (P < 0.05) such as α-sodium cholate and β-cholic acid. 3. A correlation analysis between the changes in probiotics and intestinal short-chain fatty acid metabolites after phototherapy showed that acetic acid, butyric acid, caproic acid, and propionic acid decreased and were significantly correlated with Bifidobacterium (P < 0.05). 4. After phototherapy, 17 metabolites changed significantly (P < 0.05). This correlated with many probiotics (P < 0.05). The significantly changed probiotics in this study showed a significant correlation with some intestinal metabolites (P < 0.05).ConclusionIt was found that phototherapy can significantly affect the intestinal probiotic flora and the metabolic indicators of newborns, which may be an important reason for the side effects of phototherapy, and also provides the theoretical basis for the provision of probiotics to newborns with jaundice.

The role of microbiota in autism spectrum disorder: A bibliometric analysis based on original articles.

BackgroundGastrointestinal (GI) symptoms can be observed in autism spectrum disorder (ASD) children. It is suggested that the gut microbiota and its metabolites are associated, not only with GI symptoms, but also with behaviors of ASD. The aim of this study was to explore the development context, research hotspots and frontiers of gut microbiota and ASD from January 1, 1980 to April 1, 2022 by bibliometric analysis.Materials and methodsPublications of ASD and gut microbiota research from 1 January 1980 to 1 April 2022 were retrieved from the Web of Science Core Collection (WoSCC). Publications and citations trends were analyzed by Excel 2010. CiteSpace was used to analyze countries/regions, authors, institutes, references, and keywords and to visualize the knowledge map.ResultsA total of 1027 studies were retrieved, and 266 original articles were included after screening. The most published countries and institutes were the United States and King Saud University. Afaf El-Aansary published the most articles, while Finegold SM had the highest co-citations. Hotspots and emerging trends in this area may be indicated by co-cited references and keywords and their clusters, including “gut-brain axis,” “behavior,” “chain fatty acid,” “brain,” “feces,” “propionic acid,” “clostridium perfringens,” and “species clostridium innocuum.”ConclusionThe United States dominants the research in this field, which focuses on the alterations of gut microbiota composition and its metabolites, among which the roles of the genus Clostridium and metabolites of short-chain fatty acids, especially propionic acid, are priorities. Fecal microbiota transplantation (FMT) is a promising complementary therapy. In general, research in this area is sparse, but it still has great research prospects.