Changes In Intestinal Microbiota Research Articles

Dietary Modulations in Preventing Cardiometabolic Risk in Individuals with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a complex health issue include obesity, high cholesterol, high blood pressure, and chronic inflammation that increase the risk of cardiovascular diseases (CVDs). CVDs are of great concern in the disease progression and prognosis of T2DM. This review is a comprehensive examination of the literature on the relationship between T2DM and cardiovascular risk, nutrition-related cardiometabolic risk (CMR) factors, and impact of dietary modulations on CMR. In recent years the researches has been focus on the importance of a comprehensive treatment approach like dietary modulations to address multiple cardiovascular risk reductions, including hypertension and dyslipidemia. Modulation of dietary patterns are the most promising interventions to prevent CMR factors and T2DM via affecting the body weight, glucose control, and microbial diversity of individuals. Current evidence suggests that high-quality dietary patterns such as the Dietary Approaches to Stop Hypertension (DASH) eating plan and the Mediterranean diet is important in the metabolic control processes of T2DM with anti-inflammatory and antioxidant compounds, glucagon-like peptide agonist compounds, and intestinal microbiota changes. Nutrition plays a critical role in preventing and improving CVD outcomes in patients with T2DM. Dietary modulations should be planned considering individual differences in responses to dietary composition and nutritional changes, personal preferences, eating behaviors and gut microbiota differences.

The Influence of a High-Cholesterol Diet and Forced Training on Lipid Metabolism and Intestinal Microbiota in Male Wistar Rats

Adequate experimental animal models play an important role in an objective assessment of the effectiveness of medicines and functional foods enriched with biologically active substances. The aim of our study was a comparative assessment of the effect of consumption of 1 or 2% cholesterol with and without regular (two times a week), moderate running exercise on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. In experimental rats, a response of 39 indicators (body weight, food consumption, serum biomarkers, liver composition, and changes in intestinal microbiota) was revealed. Total serum cholesterol level increased 1.8 times in animals consuming cholesterol with a simultaneous increase in low-density lipoprotein cholesterol (2 times) and decrease in high-density lipoprotein cholesterol (1.3 times) levels compared to the control animals. These animals had 1.3 times increased liver weight, almost 5 times increased triglycerides level, and more than 6 times increased cholesterol content. There was a tendency towards a decrease in triglycerides levels against the background of running exercise. The consumption of cholesterol led to a predominance of the Bacteroides family, due to a decrease in F. prausnitzii (1.2 times) and bifidobacteria (1.3 times), as well as an increase in Escherichia family (1.2 times). The running exercise did not lead to the complete normalization of microbiota.

The imbalance of pulmonary Th17/Treg cells in BALB/c suckling mice infected with respiratory syncytial virus-mediated intestinal immune damage and gut microbiota changes.

RSV is the most common pathogen causing acute lower respiratory tract infections in infants and young children, but the complex interactions between the immune system and gut microbiota induced by RSV infection still requires further research. In this study, it was suggested that RSV infection in 7-day-old BALB/c suckling mice caused lung inflammation and disruption of Th17/Treg cells development, and altered the composition of gut microbiota through IL-22 induced overexpression of RegⅢγ, leading to intestinal immune injury and disruption of gut microbiota. This research reveals that IL-22 may be the link between the lung and gut. This study may provide a new insight into the intestinal symptoms caused by RSV and other respiratory viruses and the connection between the lung and gut axis, as well as new therapeutic ideas for the treatment of RSV-infected children.

Probiotics for the prevention of gestational diabetes mellitus: A meta-analysis of randomized controlled trials.

Changes of intestinal microbiota have been shown to be involved in the development of gestational diabetes mellitus (GDM). We performed a meta-analysis to systematically evaluate the potential role of probiotics for the prevention of GDM. Systematic literature search was performed in electronic databases including PubMed, Cochrane library, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) to obtain relevant randomized controlled studies. A random-effects model was used to pool the results by incorporating the impact of the potential heterogeneity. Meta-regression and subgroup analyses were conducted to evaluate the source of heterogeneity. Fourteen studies involving 3527 pregnant women were included. Results showed that probiotics significantly reduced the incidence of GDM as compared to control (risk ratio [RR]: 0.71, 95% confidence interval [CI]: 0.52-0.96, P = 0.03) with significant heterogeneity (I2 = 73%). The meta-regression showed that body mass index (BMI) of females was positively associated with the RR for the effect of probiotics on GDM (coefficient = 0.084, P = 0.01). The results of subgroup analyses also suggested that probiotics significantly reduced the risk of GDM in women with BMI < 26 kg/m2, but not in those with BMI ≥ 26 kg/m2 (P for subgroup difference = 0.001). In addition, the preventative efficacy of probiotics on GDM was remarkable in women < 30 years, but not in those ≥ 30 years (P for subgroup difference < 0.001). In conclusion, probiotics may be effective in reducing the risk of GDM, particularly for females with lower BMI and younger age.

Efficacy and mechanism of acupuncture for functional constipation in older adults: study protocol for a randomized controlled trial.

Functional constipation (FC) is a common functional gastrointestinal disorder in clinical practice, with the prevalence of which increasing with age. With the increasing aging of the population worldwide, this problem is bound to become more prominent. Acupuncture is effective and recommended for the treatment of FC. However, little is known about how acupuncture affects the gut microbiota and inflammatory cytokines and thus improves gut function. Meanwhile, there are few high-quality clinical trials specifically focusing on acupuncture in treating FC in older people. The objective of this study is to assess the efficacy and safety of acupuncture in treating FC in older people. Additionally, the research aims to explore the mechanism of action of acupuncture in treating FC in older people by affecting intestinal microbiota and inflammation cytokines. This study is designed as a single-center, randomized, sham-controlled clinical trial. A total of 98 eligible FC patients will be randomized in a 1:1 ratio into an acupuncture group and a sham acupuncture group. Both groups will receive 24 treatments over 8 weeks with a 12-week follow-up. The primary outcome of the study is the treatment response rate, which is the proportion of participants with ≥3 mean weekly Complete Spontaneous Bowel Movements (CSBMs) over weeks 3-8. The secondary outcomes will include the proportion of participants with ≥3 mean weekly CSBMs during other assessment periods; the percentage of patients with ≥1 increase in mean weekly CSBMs from baseline; the average changes in CSBMs; Patient Assessment of Constipation-Symptoms (PAC-SYM), Bristol Stool Scale, Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and weekly usage of emergency bowel medications. Adverse events will be recorded throughout the study. Data for the outcomes will be collected at Week 0 (baseline), Week 4 (the intervention period), Week 8 (the post-treatment), Week 12 (the follow-up period) and Week 20 (the follow-up period). In addition, changes in intestinal microbiota will be analyzed using 16S rRNA high-throughput detection, and the concentration of relevant inflammatory cytokines in serum will be measured by ELISA based on blood samples. The intention-to-treat analysis will be performed in this study.Clinical trial registration: [https://www.chictr.org.cn/], identifier [ChiCTR2300070735].

Exploring the sex dimorphism in the expression of intestinal barrier and immune-related genes and intestinal microbiota in cage-cultured large yellow croaker (Larimichthys crocea) during the overwintering period along the Zhoushan coast

In Zhejiang province, large yellow croakers are primarily cultured in net cages, facing significant challenges during the overwintering period such as susceptibility to cold and starvation stress. Notably, the observable sexual dimorphism in the large yellow croaker hints at the likelihood of gender differences in their responses to these environmental stresses. However, the potential sex-specific adaptive changes during overwintering remain unexplored. To gain deeper insights, we investigated the expression of intestinal barrier-related genes, immune responses, and changes in intestinal microbiota during the overwintering period in males and females separately. The results revealed a more pronounced loss of body weight in females than that in males. In male intestines, there was a significant decrease in the expression of intestinal barrier-related genes (arp2/3, occludin, and zo1), contrasting with a significant increase in females. The expression of TLR1, TLR3, TLR7, TLR9, MyD88, and NF-κB genes in the intestines of female fish decreased significantly in March compared to November, while the opposite trend was observed in male fish. However, in the liver, TLR1, TLR3, TLR7, TLR9, MyD88, and NF-κB genes expression were both decreased significantly in males and females. In the male intestines, there was a significant increase in the expression of inflammatory cytokine genes (IL-1β and IL-6). In the females, IL-1β gene expression significantly decreased, while IL-6 expression increased significantly. The expression of IL-10 genes decreased in both males and females. In the liver, both the males and females exhibited a significant increase in the expression of IL-1β and IL-6 genes. Further analysis revealed greater susceptibility of male intestinal microbiota diversity during the overwintering period. Firmicutes’ relative abundance exhibited opposing changes between the males and females, and Proteobacteria abundance, driven by a significant increase in Vibrio bacteria, significantly increased in the males. In conclusion, the overwintering period may compromise the structural integrity of male fish intestines, reducing their immune function. Additionally, the response strategy of the intestinal microbiota differs between sexes. The findings provide crucial insights for crafting effective strategies and management decisions in cage-cultured large yellow croaker during the overwintering period, as well as offering theoretical references for monosex aquaculture.

Cefotaxime Exposure-Caused Oxidative Stress, Intestinal Damage and Gut Microbial Disruption in Artemia sinica.

Cefotaxime (CTX) is an easily detectable antibiotic pollutant in the water environment, but little is known about its toxic effects on aquatic invertebrates, especially on the intestine. Here, we determined the oxidative stress conditions of A. sinica under CTX exposure with five concentrations (0, 0.001, 0.01, 0.1 and 1 mg/L) for 14 days. After that, we focused on changes in intestinal tissue morphology and gut microbiota in A. sinica caused by CTX exposure at 0.01 mg/L. We found malondialdehyde (MDA) was elevated in CTX treatment groups, suggesting the obvious antibiotic-induced oxidative stress. We also found CTX exposure at 0.01 mg/L decreased the villus height and muscularis thickness in gut tissue. The 16S rRNA gene analysis indicated that CTX exposure reshaped the gut microbiota diversity and community composition. Proteobacteria, Actinobacteriota and Bacteroidota were the most widely represented phyla in A. sinica gut. The exposure to CTX led to the absence of Verrucomicrobia in dominant phyla and an increase in Bacteroidota abundance. At the genus level, eleven genera with an abundance greater than 0.1% exhibited statistically significant differences among groups. Furthermore, changes in gut microbiota composition were accompanied by modifications in gut microbiota functions, with an up-regulation in amino acid and drug metabolism functions and a down-regulation in xenobiotic biodegradation and lipid metabolism-related functions under CTX exposure. Overall, our study enhances our understanding of the intestinal damage and microbiota disorder caused by the cefotaxime pollutant in aquatic invertebrates, which would provide guidance for healthy aquaculture.

The Significance of Bile in the Biliopancreatic Limb on Metabolic Improvement After Duodenal-Jejunal Bypass

IntroductionDuodenal-jejunal bypass (DJB) is an experimental procedure in metabolic surgery that does not have a restrictive component. Changes in bile acid (BA) dynamics and intestinal microbiota are possibly related to metabolic improvement after DJB. Our previous studies involving obese diabetic rats showed the crucial role of the biliopancreatic limb (BPL) in metabolic improvement after DJB caused by BA reabsorption. We established a new DJB procedure to prevent bile from flowing into the BPL and aimed to elucidate the importance of bile in the BPL after DJB.MethodsOtsuka Long-Evans Tokushima Fatty rats with diabetes were divided into three groups: two DJB groups and a sham group (n = 11). Duodenal-jejunal anastomosis was performed proximal to the papilla of Vater in the DJB group (n = 11). However, the DJB-D group (n = 11) underwent a new procedure with duodenal-jejunal anastomosis distal to the papilla of Vater for preventing bile flow into the BPL.ResultsGlucose metabolism improved and weight gain was suppressed in the DJB group, but not in the DJB-D and sham groups. Serum BA level and conjugated BA concentration were elevated in the DJB group. The gut microbiota was altered only in the DJB group; the abundance of Firmicutes and Bacteroidetes decreased and that of Actinobacteria increased. However, the DJB-D group exhibited no apparent change in the gut microbiota, similar to the sham group.ConclusionBAs are essential in the BPL for metabolic improvement after DJB; they can improve the gut microbiota in these processes.Graphical

Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes—secondary analysis of a randomized placebo-controlled parallel intervention trial

BackgroundAronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes.ResultsForty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile.ConclusionIn linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions.Graphical DsmAL-oYwbuhyB_vVwEdDjVideo

Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration.

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

Postbiotics in colorectal cancer: intervention mechanisms and perspectives.

Colorectal cancer (CRC) is a common malignancy affecting the gastrointestinal tract worldwide. The etiology and progression of CRC are related to factors such as environmental influences, dietary structure, and genetic susceptibility. Intestinal microbiota can influence the integrity of the intestinal mucosal barrier and modulate intestinal immunity by secreting various metabolites. Dysbiosis of the intestinal microbiota can affect the metabolites of the microbial, leading to the accumulation of toxic metabolites, which can trigger chronic inflammation or DNA damage and ultimately lead to cellular carcinogenesis and the development of CRC. Postbiotics are preparations of inanimate microorganisms or their components that are beneficial to the health of the host, with the main components including bacterial components (e.g., exopolysaccharides, teichoic acids, surface layer protein) and metabolites (e.g., short-chain fatty acids, tryptophan metabolite, bile acids, vitamins and enzymes). Compared with traditional probiotics, it has a more stable chemical structure and higher safety. In recent years, it has been demonstrated that postbiotics are involved in regulating intestinal microecology and improving the progression of CRC, which provides new ideas for the prevention and diagnosis of CRC. In this article, we review the changes in intestinal microbiota in different states of the gut and the mechanisms of anti-tumor activity of postbiotic-related components, and discuss the potential significance of postbiotics in the diagnosis and treatment of CRC. This reviews the changes and pathogenesis of intestinal microbiota in the development of CRC, and summarizes the relevant mechanisms of postbiotics in resisting the development of CRC in recent years, as well as the advantages and limitations of postbiotics in the treatment process of CRC.

Neuroprotective Effect of a Multistrain Probiotic Mixture in SOD1G93A Mice by Reducing SOD1 Aggregation and Targeting the Microbiota-Gut-Brain Axis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. A bidirectional communication system known as the "microbiota-gut-brain" axis has a regulatory function in neurodegenerative disorders. The impact of probiotics on ALS through the "microbiota-gut-brain" axis remains uncertain. A longitudinal investigation was conducted to examine the alterations in the structure of the ileum and colon in mutant superoxide dismutase 1 (SOD1G93A) transgenic mice models of ALS by using immunofluorescence and Western blotting. Subsequently, the mice were administered a multistrain probiotic mixture (LBE) or vehicle orally, starting from 60 days of age until the terminal stage of the disease. The effects of these agents on the behavior, gut microbiota, microbial metabolites, and pathological processes of the spinal and intestine of SOD1G93A mice were analyzed, with a focus on exploring potential protective mechanisms. SOD1G93A mice exhibit various structural abnormalities in the intestine. Oral administration of LBE improved the proinflammatory response, reduced aberrant superoxide dismutase 1 (SOD1) aggregation, and protected neuronal cells in the intestine and spinal cord of SOD1G93A mice. Furthermore, LBE treatment resulted in a change in intestinal microbiota, an increase in short-chain fatty acid levels, and an enhancement in autophagy flux. SOD1G93A mice exhibited various structural abnormalities in the intestine. LBE can improve the proinflammatory response, reduce aberrant SOD1 aggregation, and protect neuronal cells in the spinal cord and intestine of SOD1G93A mice. The positive effect of LBE can be attributed to increased short-chain fatty acids and enhanced autophagy flux.

HIV-associated gut microbial alterations are dependent on host and geographic context

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men (MSM) behavior and non-MSM populations. Additionally, while we find that HIV infection is consistently associated with higher soluble markers of immune activation, most specific bacterial taxa associated with these markers in each region are not shared and none are shared across all three geographic locations in our study. Our findings demonstrate that HIV-associated changes in fecal microbiota are overall distinct among geographical locations and sexual behavior groups, although a small number of taxa shared between pairs of geographic locations warrant further investigation, highlighting the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease.

Dendrobium huoshanense Improves Lipid Metabolism Disorder by Restoring Gut Flora and Metabolites in Mice Fed a High-Fat Diet

Lipid metabolism disorders are widely acknowledged as crucial risk factors for a range of metabolic diseases, including hyperlipidemia, obesity, nonalcoholic fatty liver disease, and atherosclerosis. Dysbiosis of the gut microbiota is considered a potential mechanism of action in lipid metabolism disorders. Dendrobium huoshanense C.Z. Tang et S.J. Cheng (DH), an important edible and medicinal Chinese herb, has been shown to regulate the gut flora disorders and improve intestinal health. However, DH inhibits lipid metabolism disorders by regulating the gut flora remains unclear. Therefore, we aimed to explore the effect of the gut flora on improving blood lipid levels in mice that fed a high-fat diet supplemented with DH. Mice were randomly divided into normal control (CTR), high-fat diet (HFD), 2.25 mg/kg/day simvastatin (SIM), 300 mg/kg/day DH (LD-DH), and 600 mg/kg/day DH (HD-DH) groups for 14 weeks. Changes in serum and liver lipid levels and liver function were analyzed. Changes in intestinal microbiota and fecal metabolites were assessed using 16S rRNA gene sequencing and untargeted metabolomics. The relationships among lipids, intestinal microbiota, and fecal metabolites were analyzed using Pearson’s correlation analysis to reveal the mechanism of action of DH against lipid metabolism disorders. The results indicated that DH effectively improved the lipid profiles in both the serum and liver of HFD mice. DH was also found to alter the structure of the gut flora, especially the relative abundances of Bifidobacterium pseudolongum and B. animalis, which dramatically increased with DH. Pearson’s correlation analysis indicated that DH may mainly alter metabolites (amino acid metabolites, bile acid metabolites, lipid metabolites, etc.) to regulate lipid metabolism via the metabolic ability of the gut flora. B. pseudolongum and B. animalis may be the dominant bacterial species in the gut microbiota and play key roles in the alleviation of lipid metabolism disorders caused by HFD.

Bifidobacterium animalis subsp. lactis F1-7 Alleviates Lipid Accumulation in Atherosclerotic Mice via Modulating Bile Acid Metabolites to Downregulate Intestinal FXR.

The dysfunction of intestinal microbiota and bile acid metabolism is related to the pathogenesis of atherosclerosis. This study we explored the mechanism of Bifidobacterium animalis subsp. lactis F1-7 (Bif. animalis F1-7), improving atherosclerosis by regulating the bile acid metabolism and intestinal microbiota in the ApoE-/- mice. The Bif. animalis F1-7 effectively reduced aortic plaque accumulation and improved the serum and liver lipid levels in atherosclerotic mice. The untargeted metabolomics revealed that Bif. animalis F1-7 reduced the glycine-conjugated bile acids and the levels of differential metabolite lithocholic acid (LCA) significantly. Downregulation of LCA decreased the intestinal levels of the farnesoid X-activated receptor (FXR) and regulated the bile acid metabolism through the FXR/FGF15/CYP7A1 pathway. Furthermore, the 16srRNA gene sequencing analysis revealed that structural changes in intestinal microbiota with an increase in the abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Desulfovibrio, and a decrease in Dubosiella, Clostridium_sensu_stricto_1, and Turicibacter following the Bif. animalis F1-7 intervention. Correlation analysis showed that the changes in intestinal microbiota mentioned above were significantly correlated with bile acid metabolism in atherosclerotic mice. In conclusion, this study sheds light on the mechanisms by which Bif. animalis F1-7 regulates atherosclerosis.

Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota.

The effects of SGLT2 inhibitors on hepatic fibrosis in diabetes remain unclear. This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between gut microbiome and liver fibrosis scores or indicators of glucose metabolism. The results showed that empagliflozin intervention improved glucose metabolism and liver function with reduced liver fibrosis, which might be related to changes in intestinal microbiota. In addition, the abundance of intestinal probiotic Lactobacillus increased, while Ruminococcus and Adlercreutzia decreased after empagliflozin treatment, and correlation analysis showed that the changes in microbiota were positively correlated with liver fibrosis and glucose metabolism. Overall, considering the contribution of the gut microbiota in metabolism, empagliflozin might have improved the beneficial balance of intestinal bacteria composition. The present study provides evidence and indicates the involvement of the gut-liver axis by SGLT2 inhibitors in T2DM with liver fibrosis.

Integrated evidence of transcriptional, metabolic, and intestinal microbiota changes in Ruditapes philippinarum due to perfluorooctanoic acid-induced immunotoxicity

Perfluorooctanoic acid (PFOA) is a toxic pollutant that bioaccumulates and is a significant public health concern due to its ubiquitous and persistent occurrence in global environments. Few studies have evaluated the adverse effects of PFOA on immune system, and this is particularly true for mollusks. Here, the PFOA-associated effects on immune system were evaluated in Ruditapes philippinarum using integrated analysis of metabolomes, microbiomes, and transcriptomes, providing evidence for possible mechanisms related to immunotoxicity. PFOA exposure caused clear variation in several important metabolites related to immune regulatory function within the haemolyph from R. philippinarum, while also altering key metabolic pathways, including those of lipids, unsaturated fatty acids (UFAs), and bile acids (BAs). After exposure to PFOAs, intestinal bacterial communities also clearly changed, with the predominant microflora becoming Mycoplasma and Bacteroidetes that are related to intestinal inflammation. Molecular analyses provided consistent results, wherein the expression of immune-related genes was significantly altered. Integration of the multi-‘omics’ analyses suggested that the TLR/MyD88/NF-kB pathway, along with PI3K-Akt-mTOR pathway, PPAR-mediated lipid metabolism and the autophagy signaling pathway, likely play important roles in initiating immunotoxic effects in R. philippinarum after PFOA exposure. These results provide further evidence that PFOA exposure can lead to immunologic dysfunction and also provide new insights into the mechanisms of PFAS alteration of bivalve immune function.

Exploring the effects of dietary inulin in rainbow trout fed a high-starch, 100% plant-based diet

BackgroundHigh dietary carbohydrates can spare protein in rainbow trout (Oncorhynchus mykiss) but may affect growth and health. Inulin, a prebiotic, could have nutritional and metabolic effects, along with anti-inflammatory properties in teleosts, improving growth and welfare. We tested this hypothesis in rainbow trout by feeding them a 100% plant-based diet, which is a viable alternative to fishmeal and fish oil in aquaculture feeds. In a two-factor design, we examined the impact of inulin (2%) as well as the variation in the carbohydrates (CHO)/plant protein ratio on rainbow trout. We assessed the influence of these factors on zootechnical parameters, plasma metabolites, gut microbiota, production of short-chain fatty acids and lactic acid, as well as the expression of free-fatty acid receptor genes in the mid-intestine, intermediary liver metabolism, and immune markers in a 12-week feeding trial.ResultsThe use of 2% inulin did not significantly change the fish intestinal microbiota, but interestingly, the high CHO/protein ratio group showed a change in intestinal microbiota and in particular the beta diversity, with 21 bacterial genera affected, including Ralstonia, Bacillus, and 11 lactic-acid producing bacteria. There were higher levels of butyric, and valeric acid in groups fed with high CHO/protein diet but not with inulin. The high CHO/protein group showed a decrease in the expression of pro-inflammatory cytokines (il1b, il8, and tnfa) in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine (tjp1a and tjp3). However, the 2% inulin did not modify the expression of plasma immune markers. Finally, inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary carbohydrates.ConclusionsWith a 100% plant-based diet, inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of 2% inulin does not appear to improve the use of CHO when combined with a 100% plant-based diet.

Potato Resistant Starch Type 1 Promotes Obesity Linked with Modified Gut Microbiota in High-Fat Diet-Fed Mice.

Obesity has become a major disease that endangers human health. Studies have shown that dietary interventions can reduce the prevalence of obesity and diabetes. Resistant starch (RS) exerts anti-obesity effects, alleviates metabolic syndrome, and maintains intestinal health. However, different RS types have different physical and chemical properties. Current research on RS has focused mainly on RS types 2, 3, and 4, with few studies on RS1. Therefore, this study aimed to investigate the effect of RS1 on obesity and gut microbiota structure in mice. In this study, we investigated the effect of potato RS type 1 (PRS1) on obesity and inflammation. Mouse weights, as well as their food intake, blood glucose, and lipid indexes, were assessed, and inflammatory factors were measured in the blood and tissues of the mice. We also analyzed the expression levels of related genes using PCR, with 16S rRNA sequencing used to study intestinal microbiota changes in the mice. Finally, the level of short-chain fatty acids was determined. The results indicated that PRS1 promoted host obesity and weight gain and increased blood glucose and inflammatory cytokine levels by altering the gut microbiota structure.

Changes in intestinal microbiota and biochemical parameters in patients with inflammatory bowel disease and irritable bowel syndrome induced by the prolonged addition of soluble fibers to usual drug therapy.

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber;in addition to improving bowel movements, it maintains intestinal health by producing short-chain fatty acids. However, majority of clinical studies on PHGG have been concluded within a month and excluded usual drug therapy. Hence, this study aimed to determine the effects of long-term consumption of PHGG, in combination with drug therapy, on gut bacteria ratios, laboratory values for inflammatory response, and fecal characteristics. The study was performed in patients with irritable bowel syndrome (IBS), Crohn's disease (CD), and ulcerative colitis (UC), by the administration of PHGG for six months while they continued their usual treatment. PHGG treatment caused significant changes in patients with IBS, including an increase in the abundance of short-chain fatty acid-producing bacteria, a significant decrease in Bacteroides abundance, and normalization of the Bristol scale of stool. In patients with UC, non-significant normalization of soft stools and decrease in fecal calprotectin were observed. Adverse events were not observed in any of the groups. Thus, it would be beneficial to include PHGG in the usual drug therapies of patients with IBS. J. Med. Invest. 71 : 121-128, February, 2024.