Gut Flora Research Articles

Perturbations in gut microbiota composition in patients with autoimmune neurological diseases: a systematic review and meta-analysis

Studies suggest that gut dysbiosis occurs in autoimmune neurological diseases, but a comprehensive synthesis of the evidence is lacking. Our aim was to systematically review and meta-analyze the correlation between the gut microbiota and autoimmune neurological disorders to inform clinical diagnosis and therapeutic intervention. We searched the databases of PubMed, Embase, Web of Science, and the Cochrane Library until 1 March 2024 for research on the correlation between gut microbiota and autoimmune neurological disorders. A total of 62 studies provided data and were included in the analysis (n = 3,126 patients, n = 2,843 healthy individuals). Among the included studies, 42 studies provided data on α-diversity. Regarding α-diversity, except for Chao1, which showed a consistent small decrease (SMD = −0.26, 95% CI = −0.45 to −0.07, p < 0.01), other indices demonstrated no significant changes. While most studies reported significant differences in β-diversity, consistent differences were only observed in neuromyelitis optica spectrum disorders. A decrease in short-chain fatty acid (SCFA)-producing bacteria, including Faecalibacterium and Roseburia, was observed in individuals with autoimmune encephalitis, neuromyelitis optica spectrum disorders, myasthenia gravis, and multiple sclerosis. Conversely, an increase in pathogenic or opportunistic pathogens, including Streptococcus and Escherichia-Shigella, was observed in these patients. Subgroup analyses assessed the confounding effects of geography and immunotherapy use. These findings suggest that disturbances of the gut flora are associated with autoimmune neurological diseases, primarily manifesting as non-specific and shared microbial alterations, including a reduction in SCFA-producing bacteria and an increase in pathogenic or opportunistic pathogens.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023410215.

Electroacupuncture alleviates functional constipation by upregulating host-derived miR-205-5p to modulate gut microbiota and tryptophan metabolism

Electroacupuncture (EA) has shown promise as a treatment for Functional constipation (FC), with growing evidence suggesting it may enhance gut motility. MicroRNAs (miRNAs) serve as key regulatory molecules mediating host-microbiota interactions. However, the specific fecal miRNAs regulating microbiota composition and metabolism in EA-treated constipated mice, along with their key targets, remain unidentified. We examined fecal microbiome composition, metabolism, and colonic miRNA expression in loperamide-induced constipated mice and EA-treated mice to identify differentially expressed miRNAs and assess their relationships with microbial abundance, metabolism, and gut motility. An antibiotic cocktail and adeno-associated virus were employed to interfere with the gut microbiota and target miRNA in vivo, thereby validating the proposed mechanism. Our results indicate that miR-205-5p, significantly upregulated in fecal and colonic tissues of EA-treated constipated mice, promotes intestinal motility in a microbiome-dependent manner. Specifically, EA promoted the growth of Lactobacillus reuteri, enriched in the feces of constipation-recovered mice, through host-derived miR-205-5p regulation. Furthermore, Lactobacillus reuteri and its tryptophan metabolites (indole-3-acetamide, indole-3-acetic acid, and indole-3-carboxaldehyde) alleviated loperamide-induced constipation. These findings underscore the pivotal role of host-derived miR-205-5p in modulating microbial composition and tryptophan metabolites to enhance intestinal motility through EA.

Gut microbial dysbiosis associated to diarrheic irritable bowel syndrome can be efficiently simulated in the Mucosal ARtificial COLon (M-ARCOL)

ABSTRACT Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, with diarrhea-predominant IBS (IBS-D) as the most frequent subtype. The implication of gut microbiota in the disease’s etiology is not fully understood. In vitro gut systems can offer a great alternative to in vivo assays in preclinical studies, but no model reproducing IBS-related dysbiotic microbiota has been developed. Thanks to a large literature review, a new Mucosal ARtifical COLon (M-ARCOL) adapted to IBS-D physicochemical and nutritional conditions was set-up. To validate the model and further exploit its potential in a mechanistic study, in vitro fermentations were performed using bioreactors inoculated with stools from healthy individuals (n = 4) or IBS-D patients (n = 4), when the M-ARCOL was set-up under healthy or IBS-D conditions. Setting IBS-D parameters in M-ARCOL inoculated with IBS-D stools maintained the key microbial features associated to the disease in vivo, validating the new system. In particular, compared to the healthy control, the IBS-D model was characterized by a decreased bacterial diversity, together with a lower abundance of Rikenellaceae and Prevotellaceae, but a higher level of Proteobacteria and Akkermansiaceae. Of interest, applying IBS-D parameters to healthy stools was not sufficient to trigger IBS-D dysbiosis and applying healthy parameters to IBS-D stools was not enough to restore microbial balance. This validated IBS-D colonic model can be used as a robust in vitro platform for studies focusing on gut microbes in the absence of the host, as well as for testing food and microbiota-related interventions aimed at personalized restoration of gut microbiota eubiosis.

Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea

BackgroundDisorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.MethodsThe colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models.ResultsHere, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3β-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement.ConclusionThese findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3β-glucuronide as a key target for ameliorating BA disorder-induced diarrhea.FSirWKmfeZU8YSVhEvyAL2Video

Porphyromonas gingivalis Induces Disturbance of Kynurenine Metabolism Through the Gut-Brain Axis: Implications for Alzheimer's Disease.

Porphyromonas gingivalis is one of the major pathogens of chronic periodontitis. P. gingivalis can cause systemic inflammation, amyloid β protein deposition, and hyperphosphorylation of tau protein, leading to Alzheimer's disease (AD)-like lesions. P. gingivalis oral infection causes gut microbiota alteration, gut barrier dysfunction, and intestinal immune response and inflammation. The microbiota-gut-brain axis has a potential role in the pathogenesis of AD. Whether P. gingivalis affects AD-like lesions via the gut-brain axis needs more study. In this study, orally administered P. gingivalis induced alveolar resorption, intestinal barrier impairment, and AD-like lesions. Oral infection with P. gingivalis induced oral and gut microflora dysbiosis, imbalance of the tryptophan metabolism pathway of gut microbiota, and elevated levels of 3-hydroxykynurenine in the sera and hippocampi. The key metabolite, 3-hydroxykynurenine, suppressed Bcl2 gene expression, leading to neuronal apoptosis and promoting AD-like lesions in vivo and in vitro. These findings suggest that P. gingivalis can induce AD pathogenesis through the gut-brain axis, providing new ideas for the prevention and treatment of AD.

Effects of water acidifiers on the growth performance, intestinal function and gut microflora in broilers

ABSTRACT 1. This study evaluated the effect of acidified drinking water on the gastrointestinal function and intestinal health of broilers. 2. A total of 630 one-day-old male broilers (Arbor Acre) were randomly assigned to one of three treatment groups: drinking water treatment (CON), drinking water + 0.5 ml Selko pH®/L (Selko pH), or + 0.85 ml Forticoat®/L (Forticoat) treated groups. Performance data, gut and digesta samples were collected from the broilers at the age of 21 and 42 d. 3. The results showed that acidifying drinking water had no significant effect on body weight or average daily gain (ADG). However, addition of Forticoat significantly increased (p < 0.05) feed conversion ratio (FCR) throughout the experimental period and significantly increased (p < 0.05) pepsin activity on d 21. The Selko pH supplemented drinking water significantly increased (p < 0.05) the relative length of the duodenum and jejunum on d 21. The relative length of the jejunum and caecum on d 42 compared to birds receiving CON. The addition of the Forticoat to drinking water significantly increased (p < 0.05) the relative length of the jejunum and caecum on d 42 than for samples from birds in the CON group. In the caecal chyme, abundance of Blautia, Bifidobasterium, Faecalibacterium, Limosilactobacillus and Akkermania spp. on d 21 were significantly higher (p < 0.05) in the caecum of birds receiving Selko pH than those in CON group and the number of Escherichia Shigella in Selko pH and Forticoat group were significantly lower (p < 0.05). 4. Overall, adding Seiko pH and Forticoat to drinking water improved pepsin activity, reduced the number of caecal pathogens, increased the number of beneficial bacteria and improved intestinal health in broilers.

Life history strategies complement niche partitioning to support the coexistence of closely related Gilliamella species in the bee gut.

The maintenance of bacterial diversity at both species- and strain-levels is crucial for the sustainability of honey bee gut microbiota and host health. Periodic or random fluctuation in diet typically alters the metabolic niches available to gut microbes, thereby continuously reshaping bacterial diversity and interspecific interactions. It remains unclear how closely related bacteria adapt to these fluctuations and maintain coexistence within the bee gut. Here, we demonstrate that the five predominant Gilliamella species associated with Apis cerana, a widely distributed Asiatic honey bee, have diverged in carbohydrate metabolism to adapt to distinct nutrient niches driven by dietary fluctuation. Specifically, the glycan-specialists gain improved growth on a pollen-rich diet, but are overall inferior in competition to non-glycan-specialist on either a simple sugar or sugar-pollen diet, when co-inoculated in the bee host and transmitted across generations. Strikingly, despite of their disadvantage in a high-sugar condition, the glycan-specialists are found prevalent in natural A. cerana guts. We further reveal that these bacteria have adopted a life history strategy characterized by high biomass yield on a low-concentration sugar diet, allowing them to thrive under poor nutritional conditions, such as when the bee hosts undergo periodical starvation. Transcriptome analyses indicate that the divergence in life history strategies is attributed to gene expression programming rather than genetic variation. This study highlights the importance of integrative metabolic strategies in carbohydrate utilization, which facilitate the coexistence of closely related Gilliamella species in a changing bee gut environment.

Can an alteration of the gut microbiome increase risk of gastrointestinal malignancies? Insights from the National Inpatient Sample.

841 Background: The gut microbiome is composed of trillions of microorganisms, inhabiting the lining of the gastrointestinal (GI) tract. The gut microbiome plays multiple roles in upholding human health including maintaining metabolism and regulating immune homeostasis. Dysregulation of the gut flora is known as gut dysbiosis. Studies have shown that gut dysbiosis is linked to the development of malignancies such as colorectal cancer. The purpose of this study is to assess the correlation between an altered gut flora and development of GI malignancies. Methods: The National Inpatient Sample was queried between 2016-2020 for all adult patients with altered gut flora, defined by history of gastrointestinal/bariatric surgeries, history of clostridium difficile infection, long-term antibiotic use, and inflammatory bowel disease. Rates of various cancers were compared between this cohort and all other patients utilizing chi-squared tests. Binary logistic regressions were utilized to calculate odds ratios of developing the various cancers, adjusted for age, sex, Charlson Comorbidity Index (CCI), and smoking status. Results: A total of 7,758,168 hospitalizations with altered gut flora were identified. Esophageal cancer (aOR 3.16, 95% CI 3.08 - 3.24) and colorectal cancer (aOR 3.15, 95% CI 3.11 - 3.18) were observed to have the highest odds of occurring in patients with altered gut flora. Gastric, hepatobiliary, pancreatic, and neuroendocrine cancers also all had significantly higher odds of occurring in patients with altered gut flora. Conclusions: Our study shows that conditions altering the gut flora are associated with increased odds of malignancies of the GI tract. This suggests that the gut microbiome may play an intricate role in regulation of tumor cell proliferation. Optimization of gut health and restoration of gut flora may prove beneficial to patients at high risk for malignancies of the GI tract. Altered Gut Flora (%) Intact Gut Flora (%) Adjusted Odds Ratio (CI) p-value Esophageal 0.4 0.1 3.16 (3.08 - 3.24) &lt;.001 Gastric 0.3 0.1 1.67 (1.64-1.69) &lt;.001 Colorectal 2.5 0.6 3.15 (3.11 - 3.18) &lt;.001 Hepatobiliary 0.4 0.3 1.04 (1.02 - 1.07) &lt;.001 Pancreatic 0.6 0.3 1.34 (1.31 - 1.37) &lt;.001 Neuroendocrine 0.2 0.1 1.38 (1.33 - 1.44) &lt;.001

Konjac glucomannan and κ-carrageenan improve hepatic fatty acid metabolism and colonic microbiota in suckling piglet.

Konjac glucomannan (KGM) and κ-carrageenan are polysaccharides that have garnered attention for their potential health benefits. This study aimed to evaluate the maternal supplementation of KGM and κ-carrageenan (SF) during later gestation and lactation on the effect of hepatic lipid metabolism and colonic microflora in offspring. Regarding antioxidant and inflammatory factors in the suckling piglet liver, our results showed that nuclear factor erythroid 2-related factor 2 (Nrf2) and interleukin (IL)-10 levels were significantly increased in the SF group (P<0.05). In liver mitochondrial function, the mRNA levels of voltage-dependent anion channel 1 (VDAC1), fission 1 (Fis1), and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) were significantly up-regulated in the SF group compared to the control (Con) group (P<0.05). The mRNA level of peroxisome proliferator-activated receptor alpha (PPARα) was remarkably down-regulated in the SF group (P<0.05). In the colonic microflora of suckling piglets, we found that the SF group increased the abundance of Megasphaera and reduced the abundance of Erysipelotrichaceae_unclassified. The occludin level was significantly increased in the SF group than in the Con group (P<0.05). In summary, maternal supplementation with SF improves hepatic lipid metabolism and colonic microflora in suckling piglets.

3,3'-Diindolylmethane improves pathology and neurological outcome following traumatic brain injury.

3,3'-Diindolylmethane (DIM), a naturally occurring bis-indole found in cruciferous vegetables and produced in small amounts in the normal flora of the human gut, has demonstrated neuroprotective benefits in models of CNS hypoxia and stroke. In the CNS, DIM modulates the activation of the aryl hydrocarbon receptor (AhR) and inhibits its pro-inflammatory effects. Although capable of crossing the blood brain barrier, DIM's bioavailability is limited by its low solubility. Dispersed BR4044 provides a nanoscale high-solubility DIM suspension with the potential for treating traumatic brain injury (TBI). The present study aimed to determine whether BR4044 treatment could reduce pathology and improve behavioral recovery following moderate TBI. Male Sprague Dawley rats received moderate fluid percussion injury or sham surgery followed by vehicle or BR4044 treatment in the acute recovery period. TBI BR4044 animals showed significantly reduced cortical and hippocampal edema and lower levels of serum-derived extracellular vesicles compared to TBI Vehicle animals. BR4044 treatment of TBI animals preserved sensorimotor function and associative fear memory. Cortical contusion size and neuronal loss in the parietal cortex and CA3 region of the hippocampus were also significantly reduced with BR4044 treatment. BR4044 also decreased microbleeding and nuclear AhR at the contusion site. This translational study demonstrates that BR4044 ameliorates pathology and improves neurological outcomes following TBI by reducing brain edema, lowering acute extracellular vesicle release, modulating AhR, preserving cortical and hippocampal neurons, reducing red blood cell (RBC) extravasation into the injured brain, and promoting behavioral recovery.

Effects of drinking water supplemented with apple vinegar, essential oils, or colistin sulfate on growth performance, blood lipids, antioxidant status, intestinal morphology, and gut microflora of broiler chickens.

With rising concerns about antibiotic resistance and its consequences on public health, the identification of safe and effective alternatives to antibiotics in the poultry industry has become increasingly critical. This study aimed to evaluate the effects of supplementing drinking water with apple vinegar and essential oils, compared to an antibiotic growth promoter, on the growth performance, serum lipid profile, antioxidant status, intestinal morphology, and gastrointestinal microflora population of broiler chickens. A total of 240 one-day-old male broiler chickens were randomly assigned to four treatments, each consisting of six replicate pens with ten birds per pen. The broiler chickens received the following experimental treatments: normal drinking water without additives (control) and drinking water supplemented with antibiotic (0.25 ml/L), apple vinegar (1 ml/L), and essential oils blend (0.5 ml/L). The results showed that adding antibiotic or essential oils blend to drinking water improved body weight gain and feed conversion ratio throughout the entire rearing period (P < 0.05). The serum levels of cholesterol and low-density lipoprotein in broilers that received apple vinegar or essential oils blend were lower than those in the control and antibiotic groups (P < 0.05). The essential oils blend treatment significantly increased the activity of glutathione peroxidase and superoxide dismutase in the serum of broiler chickens compared to the other treatments (P < 0.05). Furthermore, adding essential oils blend to the drinking water increased villus height and villus height to crypt depth ratio in the jejunum of broilers (P < 0.05). The broiler chickens in the apple vinegar and essential oil blend groups also exhibited a lower population of Enterobacteriaceae and a higher count of lactic acid bacteria in the ceca (P < 0.05). In summary, the addition of essential oils blend to the drinking water of broiler chickens has beneficial effects on production performance and can serve as an effective alternative to antibiotic growth promoters.

Alpha synuclein overexpression can drive microbiome dysbiosis in mice

Growing evidence indicates that persons with Parkinson disease (PD), have a unique composition of indigenous gut microbes. Given the long prodromal or pre-diagnosed period, longitudinal studies of the human and rodent gut microbiome before symptomatic onset and for the duration of the disease are currently lacking. PD is partially characterized by the accumulation of the protein α-synuclein (α-syn) into insoluble aggregates, in both the central and enteric nervous systems. As such, several experimental rodent and non-human primate models of α-syn overexpression recapitulate some of the hallmark pathophysiologies of PD. These animal models provide an opportunity to assess how the gut microbiome changes with age under disease-relevant conditions. Here, we used a transgenic mouse strain, which overexpress wild-type human α-syn to test how the gut microbiome composition responds in this model of PD pathology during aging. Using shotgun metagenomics, we find significant, age and genotype-dependent bacterial taxa whose abundance becomes altered with age. We reveal that α-syn overexpression can drive alterations to the gut microbiome composition and suggest that it limits diversity through age. Taxa that were most affected by genotype-age interaction were Lactobacillus and Bifidobacteria. In a mouse model, we showed direct link between alpha synuclein geneotype (hallmark of PD), a dysbiotic and low-diversity gut microbiome, and dysbiotic levels of Bifidobacteria and Lactobacillus (most robust features of PD microbiome). Given emerging data on the potential contributions of the gut microbiome to PD pathologies, our data provide an experimental foundation to understand how the PD-associated microbiome may arise as a trigger or co-pathology to disease.

A human gut bacterium antagonizes neighboring bacteria by altering their protein-folding ability.

Antagonistic interactions play a key role in determining microbial community dynamics. Here, we report that one of the most widespread contact-dependent effectors in human gut microbiomes, Bte1, directly targets the PpiD-YfgM periplasmic chaperone complex in related microbes. Structural, biochemical, and genetic characterization of this interaction reveals that Bte1 reverses the activity of the chaperone complex, promoting substrate aggregation and toxicity. Using Bacteroides, we show that Bte1 is active in the mammalian gut, conferring a fitness advantage to expressing strains. Recipient cells targeted by Bte1 exhibit sensitivity to membrane-compromising conditions, and human gut microbes can use this effector to exploit pathogen-induced inflammation in the gut. Further, Bte1 allelic variation in gut metagenomes provides evidence for an arms race between Bte1-encoding and immunity-encoding strains in humans. Together, these studies demonstrate that human gut microbes alter the protein-folding capacity of neighboring cells and suggest strategies for manipulating community dynamics.

Impact of C/N/P dietary nutrient on manure characteristics: Pollutant fractions and microbial community.

Regulation of labile fraction of excreted manure represents a promising advance for environmental pollution mitigation. However, investigation of the properties of various pollutant fractions within manure and potential influence of dietary nutrient fractions on the release of labile manure remains unclear. Feeding trials involving pigs at three distinct growth stages fed by diets with nine different energy levels were conducted and the characteristics of labile manure generated under various treatments based on nutrient profiles were analyzed. The impact of dietary nutrient fractions on variables such as labile manure pollutants, pig performance, manure weight and dominant microorganisms were evaluated via theoretical modeling and correlation analysis. The results indicated that critical dietary nutrient factors such as dietary C fraction, protein N-materials and dietary P fraction varied respectively with pig growth stages. The labile manure composition and proportion were influenced by dietary C/N/P fractions and indigestible components, through regulation of the structure of the gut microbiota and the relative abundance of gut microbes. This study finds that initiating dietary regulatory measures could effectively control the release of labile manure and reduce its proportion in the overall manure and thus, provides a novel approach to achieve manure source pollution control, ensure environmental-friendly diet formula and mitigate manure-related environmental pollution.

Profiling the response of individual gut microbes to free fatty acids (FFAs) found in human milk

Profiling the response of individual gut microbes to free fatty acids (FFAs) found in human milk

Lactobacillus johnsonii Generates Cyclo(pro-trp) and Promotes Intestinal Ca2+ Absorption to Alleviate CKD-SHPT.

Patients with chronic kidney disease (CKD) are at a high risk of developing secondary hyperparathyroidism (SHPT), which may cause organ dysfunction and increase patient mortality. The main clinical interventions for CKD-SHPT involve calcium supplements to boost absorption, but ineffective for some patients, and the reasons remain unclear. Here, CKD mice are divided into high and low groups based on intact parathyroid hormone (iPTH) levels. The high group exhibits significant changes in gut microbes, including a decrease in Lactobacillus, an increase in parathyroid hyperplasia, and a decrease in intestinal calcium. Fecal microbiota transplantation and L. johnsonii colonization indicate a link between gut microbes and CKD-SHPT. Clinically, higher L. johnsonii levels are correlated with milder hyperparathyroidism CKD-SHPT. The receiver operating characteristic (ROC) curve for L. johnsonii abundance and surgical risk is 0.81, with the calibration curve confirming predictive accuracy, and decision curve analysis revealing good clinical applicability. In vivo and in vitro experiments show that cyclo(pro-trp) enhance calcium inflow and lower iPTH levels in intestinal epithelial cells via a calcium-sensing receptor and transient receptor potential vanilloid 4 pathways. This study identified the crucial role of L. johnsonii in CKD-SHPT, unveiling a new mechanism for calcium imbalance and offering novel strategies for SHPT treatment and drug development.

Microbial remodeling of gut tryptophan metabolism and indole-3-lactate production regulate epithelial barrier repair and viral suppression in human and simian immunodeficiency virus infections.

Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an in vivo simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, ex vivo HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are associated with mucosal barrier disruption and immune suppression. Administration of Lactiplantibacillus plantarum or Bifidobacterium longum subsp. infantis into the SIV-inflamed gut lumen in vivo resulted in rapid reprogramming of microbial TRP metabolism towards indole-3-lactic acid (ILA) production. This shift accelerated epithelial repair and enhanced anti-viral defenses through induction of IL-22 signaling in mucosal T cells and aryl hydrocarbon receptor activation. Additionally, ILA treatment of human colorectal tissue explants ex vivo inhibited HIV replication by reducing mucosal inflammatory cytokine production and cell activation. Our findings underscore the therapeutic potential of microbial metabolic reprogramming of TRP-to-ILA and mechanisms in mitigating viral pathogenic effects and bolstering mucosal defenses for HIV eradication.

Macronutrient balance determines the human gut microbiome eubiosis: insights from in vitro gastrointestinal digestion and fermentation of eight pulse species

The interactions between macronutrients, the human gut microbiome, and their metabolites (short-chain fatty acids) were comprehensively investigated via an in vitro digestion and fermentation model subjected to eight pulse species. 16S rRNA sequencing and taxonomic analysis of pulse digesta fermented for up to 24 h revealed an increase in the relative abundance of gut health-detrimental genera represented by Escherichia-Shigella in kidney bean, soybean, cowpea, chickpea, and black bean samples. In contrast, the relative abundance of health-positive genera, including Bacteroides, Eubacterium, and Akkermansia, was elevated in red bean, mung bean, and Heunguseul. At the same time, the proportion of the pathogenic Escherichia-Shigella decreased. Concurrently, these three species exhibited an increase in microbial diversity as evidenced by the calculation of α-diversity (Shannon index) and β-diversity (Bray-Curtis distance). Despite the lower nutrient contents in the three pulses, represented by carbohydrates, amino acids, and fatty acids, network analysis revealed that the nutrient contents in the pulse digesta possess complex positive or negative correlations with a variety of bacteria, as well as their metabolites. These correlations were more pronounced in red bean, mung bean, and Heunguseul than in the other pulses. It was postulated that the overall potential to nourish gut environments in these species was due to the balance of their nutritional components. The linear regression analysis demonstrated that there was a negative association between carbohydrate and amino acid contents and the increase in Shannon indices. Furthermore, the ratio of carbohydrates to fatty acids and amino acids to fatty acids displayed negative correlations with the diversity increase. The ratio of carbohydrates to amino acids showed a weak positive correlation. It is noteworthy that a diet comprising foods with a balanced nutritional profile supports the growth of beneficial gut microbes, thereby promoting microbial eubiosis. Consistent work on different ingredients is essential for precise insight into the interplay between food and the human microbiome in complex dietary patterns.

Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder

Attention Deficit Hyperactivity Disorder (ADHD) is a clinically common neurodevelopmental disorder of the brain. In addition to genetic factors, an imbalance in gut flora may also play a role in the development of ADHD. Currently, it is critical to investigate the function of gut flora and related metabolites, which may form the fundamental basis of bidirectional cross-linking between the brain and the gut, in addition to focusing on the changed gut flora in ADHD. This study aimed to investigate the possible relationship between changes in gut flora and metabolites and ADHD by analyzing metagenome and untargeted metabolomics of fecal samples from ADHD patients. Specifically, we attempted to identify key metabolites and the metabolic pathways they are involved in, as well as analyze in detail the structure and composition of the gut flora of ADHD patients. In order to further investigate the relationship between gut flora and ADHD symptoms, some behavioral studies were conducted following the transplantation of gut flora from ADHD patients into rats. The results of the metagenome analysis revealed several distinct strains, including Bacteroides cellulosilyticus, which could be important for diagnosing ADHD. Additionally, the ADHD group showed modifications in several metabolic pathways and metabolites, including the nicotinamide and nicotinic acid metabolic pathways and the metabolite nicotinamide in this pathway. The behavioral results demonstrated that rats with ADHD gut flora transplants displayed increased locomotor activity and interest, indicating that the onset of behaviors such as ADHD could be facilitated by the flora associated with ADHD. This research verified the alterations in gut flora and metabolism observed in ADHD patients and provided a list of metabolites and flora that were significantly altered in ADHD. Simultaneously, our findings revealed that modifications to the microbiome could potentially trigger behavioral changes in animals, providing an experimental basis for comprehending the function and influence of gut flora on ADHD. These results might provide new perspectives for the development of novel treatment strategies.

Protective Effects of Black Rice Anthocyanins on D-Galactose-Induced Renal Injury in Mice: The Role of Nrf2 and NF-κB Signaling and Gut Microbiota Modulation

Background/Objectives: This study aimed to evaluate the renal protective effects of black rice anthocyanins (BRAs) against renal injury in mice induced by D-galactose (D-gal). Methods: The renal aging mouse model was established by thirteen consecutive weeks of subcutaneous injections of D-gal. The serum levels of urea nitrogen (BUN), creatinine (CRE), uric acid (UA), antioxidant enzymes (e.g., GSH-Px and SOD), and total antioxidant capacity (T-AOC), as well as the contents of inflammatory factors (IL-1β, IL-6, and TNF-α) in kidney tissues were evaluated. Additionally, the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins was examined. Results: BRA treatment significantly reduced serum levels of BUN, and CRE increased the concentrations of antioxidant enzymes and total antioxidant capacity in renal tissues, and reduced the levels of inflammatory factors. Furthermore, BRAs restored the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins to normal levels and promoted the recovery of the renal tissue architecture. Conclusions: It was demonstrated that BRAs could potentially prevent and protect against kidney injury by modulating the Nrf2 and NF-κB signaling pathways, attenuating oxidative stress and inflammatory responses, and modulating the gut microflora. These findings provide a scientific basis for the application of BRAs as a natural bioactive substance in the field of nephroprotection, especially against the renal degeneration that accompanies the aging process.