Microbiota in different digestive tract of paddlefish (Polyodon spathula) are related to their functions.

Paddlefish has high economic and ecological value. In this study, microbial diversity and community structure in intestine, stomach, and mouth of paddlefish were detected using high-throughput sequencing. The results showed that the diversity and richness indices decreased along the digestive tract, and significantly lower proportion of those were observed in intestine. Firmicutes, Bacteroidetes and Proteobacteria were the dominant phyla. In top 10 phyla, there was no significant difference in mouth and stomach. But compared with intestine, there were significant differences in 8 of the 10 phyla, and Firmicutes and Bacteroidetes increased significantly, while Proteobacteria decreased significantly. There was no dominant genus in mouth and stomach, but Clostridium_sensu_stricto_1 and uncultured_bacterium_o_Bacteroidales was predominant in intestine. In conclusion, the species and abundance of microbiota in the mouth and stomach of paddlefish were mostly the same, but significantly different from those in intestine. Moreover, there was enrichment of the dominant bacteria in intestine.

A comparative study on the detection of Mycobacterium leprae DNA in urine samples of leprosy patients using Rlep-PCR with other conventional samples.

BACKGROUND: Mycobacterium leprae causes leprosy that is highly stigmatized and chronic infectious skin disease. Only some diagnostic tools are being used for the identification M. leprae in clinical samples, such as bacillary detection, and histopathological tests. These methods are invasive and often have low sensitivity. Currently, the PCR technique has been used as an effective tool fordetecting M. leprae DNA across different clinical samples. The current study aims to detect M. leprae DNA in urine samples of untreated and treated leprosy patients using the Rlep gene (129 bp) and compared the detection among Ridley-Jopling Classification. METHODS: Clinical samples (Blood, Urine, and Slit Skin Smears (SSS)) were collected from leprosy and Non-leprosy patients. DNA extraction was performed using standard laboratory protocol and Conventional PCR was carried out for all samples using Rlep gene target and the amplicons of urine samples were sequenced by Sanger sequencing to confirm the Rlep gene target. RESULTS: The M. leprae DNA was successfully detected in all clinical samples across all types of leprosy among all the study groups using RLEP-PCR. Rlep gene target was able to detect the presence of M. leprae DNA in 79.17% of urine, 58.33% of blood, and 50% of SSS samples of untreated Smear-Negative leprosy patients. The statistical significant difference (p = 0.004) was observed between BI Negative (Slit Skin Smear test) and RLEP PCR positivity in urine samples of untreated leprosy group. CONCLUSION: The PCR positivity using Rlep gene target (129 bp) was highest in all clinical samples among the study groups, across all types of leprosy. Untreated tuberculoid and PNL leprosy patients showed the highest PCR positivity in urine samples, indicating its potential as a non-invasive diagnostic tool for leprosy and even for contact screening.

In silico analysis of intestinal microbial instability and symptomatic markers in mice during the acute phase of severe burns.

BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.

Modeling Dynamics of Human Gut Microbiota Derived from Gluten Metabolism: Obtention, Maintenance and Characterization of Complex Microbial Communities.

Western diets are rich in gluten-containing products, which are frequently poorly digested. The human large intestine harbors microorganisms able to metabolize undigested gluten fragments that have escaped digestion by human enzymatic activities. The aim of this work was obtaining and culturing complex human gut microbial communities derived from gluten metabolism to model the dynamics of healthy human large intestine microbiota associated with different gluten forms. For this purpose, stool samples from six healthy volunteers were inoculated in media containing predigested gluten or predigested gluten plus non-digested gluten. Passages were carried out every 24 h for 15 days in the same medium and community composition along time was studied via V3-V4 16S rDNA sequencing. Diverse microbial communities were successfully obtained. Moreover, communities were shown to be maintained in culture with stable composition for 14 days. Under non-digested gluten presence, communities were enriched in members of Bacillota, such as Lachnospiraceae, Clostridiaceae, Streptococcaceae, Peptoniphilaceae, Selenomonadaceae or Erysipelotrichaceae, and members of Actinomycetota, such as Bifidobacteriaceae and Eggerthellaceae. Contrarily, communities exposed to digested gluten were enriched in Pseudomonadota. Hence, this study shows a method for culture and stable maintenance of gut communities derived from gluten metabolism. This method enables the analysis of microbial metabolism of gluten in the gut from a community perspective.

The Human Gut and Dietary Salt: The Bacteroides/Prevotella Ratio as a Potential Marker of Sodium Intake and Beyond.

The gut microbiota is a dynamic ecosystem that plays a pivotal role in maintaining host health. The perturbation of these microbes has been linked to several health conditions. Hence, they have emerged as promising targets for understanding and promoting good health. Despite the growing body of research on the role of sodium in health, its effects on the human gut microbiome remain under-explored. Here, using nutrition and metagenomics methods, we investigate the influence of dietary sodium intake and alterations of the human gut microbiota. We found that a high-sodium diet (HSD) altered the gut microbiota composition with a significant reduction in Bacteroides and inverse increase in Prevotella compared to a low-sodium diet (LSD). However, there is no clear distinction in the Firmicutes/Bacteroidetes (F/B) ratio between the two diet types. Metabolic pathway reconstruction revealed the presence of sodium reabsorption genes in the HSD, but not LSD. Since it is currently difficult in microbiome studies to confidently associate the F/B ratio with what is considered healthy (e.g., low sodium) or unhealthy (e.g., high sodium), we suggest that the use of a genus-based ratio such as the Bacteroides/Prevotella (B/P) ratio may be more beneficial for the application of microbiome studies in health.

Intestinal microbiome profiles in broiler chickens raised without antibiotics exhibit altered microbiome dynamics relative to conventionally raised chickens.

The present study was undertaken to profile and compare the cecal microbial communities in conventionally (CONV) grown and raised without antibiotics (RWA) broiler chickens. Three hundred chickens were collected from five CONV and five RWA chicken farms on days 10, 24, and 35 of age. Microbial genomic DNA was extracted from cecal contents, and the V4-V5 hypervariable regions of the 16S rRNA gene were amplified and sequenced. Analysis of 16S rRNA sequence data indicated significant differences in the cecal microbial diversity and composition between CONV and RWA chickens on days 10, 24, and 35 days of age. On days 10 and 24, CONV chickens had higher richness and diversity of the cecal microbiome relative to RWA chickens. However, on day 35, this pattern reversed such that RWA chickens had higher richness and diversity of the cecal microbiome than the CONV groups. On days 10 and 24, the microbiomes of both CONV and RWA chickens were dominated by members of the phylum Firmicutes. On day 35, while Firmicutes remained dominant in the RWA chickens, the microbiome of CONV chickens exhibited am abundance of Bacteroidetes. The cecal microbiome of CONV chickens was enriched with the genus Faecalibacterium, Pseudoflavonifractor, unclassified Clostridium_IV, Bacteroides, Alistipes, and Butyricimonas, whereas the cecal microbiome of RWA chickens was enriched with genus Anaerofilum, Butyricicoccu, Clostridium_XlVb and unclassified Lachnospiraceae. Overall, the cecal microbiome richness, diversity, and composition were greatly influenced by the management program applied in these farms. These findings provide a foundation for further research on tailoring feed formulation or developing a consortium to modify the gut microbiome composition of RWA chickens.

Acute Impacts of Ionizing Radiation Exposure on the Gastrointestinal Tract and Gut Microbiome in Mice.

Radiation therapy for abdominopelvic malignancies often results in damage to the gastrointestinal tract (GIT) and permanent changes in bowel function. An overlooked component of the pathophysiology of radiation-induced bowel injury is the role of the gut microbiome. The goal of this research was to identify the impacts of acute radiation exposure on the GIT and gut microbiome. C57BL/6 mice exposed to whole-body X-rays (0.1-3 Gy) were assessed for histological and microbiome changes 48 h post-radiation exposure. Within the ileum, a dose of 3 Gy significantly decreased crypt depth as well as the number of goblet cells, but increased overall goblet cell size. Overall, radiation altered the microbial distribution within each of the main phyla in a dose- and tissue-dependent manner. Within the Firmicutes phylum, high dose irradiation resulted in significant alterations in bacteria from the class Bacilli within the small bowels, and from the class Clostridia in the large bowels. The 3 Gy radiation also significantly increased the abundance of bacterial families from the Bacteroidetes phylum in the colon and feces. Overall, we identified various alterations in microbiome composition following acute radiation exposure, which could potentially lead to novel biomarkers for tracking patient toxicities or could be used as targets for mitigation strategies against radiation damage.

Multi-Omics Analysis of Gut Microbiota and Host Transcriptomics Reveal Dysregulated Immune Response and Metabolism in Young Adults with Irritable Bowel Syndrome.

The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the associations among gut microbiota and host transcriptomics in young adults with IBS. Stool and peripheral blood samples from 20 IBS subjects and 21 healthy controls (HCs) collected at the baseline visit of an RCT were sequenced to depict the gut microbiota and transcriptomic profiles, respectively. The diversities, composition, and predicted metabolic pathways of gut microbiota significantly differed between IBS subjects and HCs. Nine genera were significantly abundant in IBS stool samples, including Akkermansia, Blautia, Coprococcus, Granulicatella, Holdemania, Oribacterium, Oscillospira, Parabacteroides, and Sutterella. There were 2264 DEGs found between IBS subjects and HCs; 768 were upregulated, and 1496 were downregulated in IBS participants compared with HCs. The enriched gene ontology included the immune system process and immune response. The pathway of antigen processing and presentation (hsa04612) in gut microbiota was also significantly different in the RNA-seq data. Akkermansia, Blautia, Holdemania, and Sutterella were significantly correlated with ANXA2P2 (upregulated, positive correlations), PCSK1N (downregulated, negative correlations), and GLTPD2 (downregulated, negative correlations). This study identified the dysregulated immune response and metabolism in IBS participants revealed by the altered gut microbiota and transcriptomic profiles.

Performance evaluation of machine-assisted interpretation of Gram stains from positive blood cultures.

Manual microscopy of Gram stains from positive blood cultures (PBCs) is crucial for diagnosing bloodstream infections but remains labor intensive, time consuming, and subjective. This study aimed to evaluate a scan and analysis system that combines fully automated digital microscopy with deep convolutional neural networks (CNNs) to assist the interpretation of Gram stains from PBCs for routine laboratory use. The CNN was trained to classify images of Gram stains based on staining and morphology into seven different classes: background/false-positive, Gram-positive cocci in clusters (GPCCL), Gram-positive cocci in pairs (GPCP), Gram-positive cocci in chains (GPCC), rod-shaped bacilli (RSB), yeasts, and polymicrobial specimens. A total of 1,555 Gram-stained slides of PBCs were scanned, pre-classified, and reviewed by medical professionals. The results of assisted Gram stain interpretation were compared to those of manual microscopy and cultural species identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The comparison of assisted Gram stain interpretation and manual microscopy yielded positive/negative percent agreement values of 95.8%/98.0% (GPCCL), 87.6%/99.3% (GPCP/GPCC), 97.4%/97.8% (RSB), 83.3%/99.3% (yeasts), and 87.0%/98.5% (negative/false positive). The assisted Gram stain interpretation, when compared to MALDI-TOF MS species identification, also yielded similar results. During the analytical performance study, assisted interpretation showed excellent reproducibility and repeatability. Any microorganism in PBCs should be detectable at the determined limit of detection of 105 CFU/mL. Although the CNN-based interpretation of Gram stains from PBCs is not yet ready for clinical implementation, it has potential for future integration and advancement.

Tartrate fermentation with H2 production by a new member of Sporomusaceae enriched from rice paddy soil.

In rice paddies, soil and plant-derived organic matter are degraded anaerobically to methane (CH4), a powerful greenhouse gas. The highest rate of methane emission occurs during the reproductive stage of the plant when mostly dicarboxylic acids are exudated by the roots. The emission of methane at this stage depends largely on the cooperative interaction between dicarboxylic acid-fermenting bacteria and methanogenic archaea in the rhizosphere. The fermentation of tartrate, one of the major acids exudated, has been scarcely explored in rice paddy soils. In this work, we characterized an anaerobic consortium from rice paddy soil composed of four bacterial strains, whose principal member (LT8) can ferment tartrate, producing H2 and acetate. Tartrate fermentation was accelerated by co-inoculation with a hydrogenotrophic methanogen. The assembled genome of LT8 possesses a Na+-dependent oxaloacetate decarboxylase and shows that this bacterium likely invests part of the H2 produced to reduce NAD(P)+ to assimilate C from tartrate. The phylogenetic analysis of the 16S rRNA gene, the genome-based classification as well as the average amino acid identity (AAI) indicated that LT8 belongs to a new genus within the Sporomusaceae family. LT8 shares a few common features with its closest relatives, for which tartrate degradation has not been described. LT8 is limited to a few environments but is more common in rice paddy soils, where it might contribute to methane emissions from root exudates.IMPORTANCEThis is the first report of the metabolic characterization of a new anaerobic bacterium able to degrade tartrate, a compound frequently associated with plants, but rare as a microbial metabolite. Tartrate fermentation by this bacterium can be coupled to methanogenesis in the rice rhizosphere where tartrate is mainly produced at the reproductive stage of the plant, when the maximum methane rate emission occurs. The interaction between secondary fermentative bacteria, such as LT8, and methanogens could represent a fundamental step in exploring mitigation strategies for methane emissions from rice fields. Possible strategies could include controlling the activity of these secondary fermentative bacteria or selecting plants whose exudates are more difficult to ferment.

Gut dysbiosis is linked to metabolic syndrome in obese Egyptian women: potential treatment by probiotics and high fiber diets regimen.

Metabolic syndrome (MetS) is defined as a cluster of glucose intolerance, hypertension, dyslipidemia, and central obesity with insulin resistance. The role of gut microbiota in metabolic disorders is increasingly considered. To investigate the effects of probiotic supplements and hypocaloric high fiber regimen on MetS in obese Egyptian women. A longitudinal follow-up intervention study included 58 obese Egyptian women, with a mean age of 41.62 ± 10.70 years. They were grouped according to the criteria of MetS into 2 groups; 23 obese women with MetS and 35 ones without MetS. They followed a hypocaloric high fiber regimen weight loss program, light physical exercise, and received a probiotic supplement daily for 3 months. For each participating woman, blood pressure, anthropometric measurements, basal metabolic rate (BMR), dietary recalls, laboratory investigations, and microbiota analysis were acquired before and after 3 months of follow-up. After intervention by the probiotic and hypocaloric high fiber regimen and light exercise, reduction ranged from numerical to significant difference in the anthropometric parameters, blood pressure, and BMR was reported. All the biochemical parameters characterized by MetS decreased significantly at p ≤ 0.05-0.01. Before the intervention, results revealed abundant of Bacteroidetes bacteria over Firmicutes with a low Firmicutes/Bacteroidetes ratio. After the intervention, Log Lactobacillus, Log Bifidobacteria, and Log Bacteroidetes increased significantly in both groups, while Log Firmicutes and the Firmicutes/Bacteroidetes Ratio revealed a significant decrease. In conclusion, this study's results highlight a positive trend of probiotics supplementation with hypocaloric high-fiber diets in amelioration of the criteria of the Mets in obese Egyptian women.

Unraveling the functional characteristics of endophytic bacterial diversity for plant growth promotion and enhanced secondary metabolite production in Pelargonium graveolens.

The rich diversity of microbial endophytic communities associated with plants, often referred to as the second genome, serves as a compelling illustration of efficient co-evolution. This noteworthy partnership plays a pivotal role in sustaining plant well-being and enhancing plant adaptability across diverse habitats. Therefore, examining the diversity of endophytic microbes associated with their particular host plant is valuable for gaining insights into the vast spectrum of plant-microbe interactions. The present experiments aimed at investigating the bacterial endophytic diversity in both root and shoot tissues of Pelargonium graveolens, employing culture dependent and culture independent high-throughput metagenomics approach. A total of 614 and 620 operational taxonomic units (OTUs), encompassing 291 and 229 genera, were identified in the shoot and root tissues of P. graveolens, respectively. Furthermore, the subsequent classification of OTUs revealed 15 highly abundant phyla, with Proteobacteria dominating both root and shoot tissues. Notably, an exceptionally high abundance of Firmicutes phyla was observed in the shoot compared to the root. Additionally, 30 bacterial endophytes from the root, stem, petiole, and leaves were isolated and molecularly characterized, unveiling a consistent pattern of diversity distribution between the root and shoot of P. graveolens. Upon screening all isolates for plant growth promoting traits, Pseudomonas oryzihabitans was found to be positive for major biochemical test like nitrogen fixation, phosphate solubilization etc. and on inoculation resulted in about two-fold increase in content of essential oil accompanied by a significant rise in the geraniol and citronellol content. Diving deep into the genetic constitution of P. oryzihabitans unveiled a substantial number of genes directly and indirectly contributing to the endophyte's capability in colonizing host plants effectively. In summary, data obtained from metagenomics and culture dependent approaches including glass house trials suggest potential bacterial endophytes suitable for field applications for yield enhancement and in planta secondary metabolite enhancement investigations.

Palmitoleic Acid Ameliorates Metabolic Disorders and Inflammation by Modulating Gut Microbiota and Serum Metabolites.

SCOPE: Palmitoleic acid (POA) is an omega-7 monounsaturated fatty acid that has been suggested to improve metabolic disorders. However, it remains unclear whether gut microbiota plays a role in the amelioration of metabolic disorders by POA. This study aims to investigate the regulation of POA on metabolism, as well as systemic inflammation in HFD-fed mice from the perspective of serum metabolome and gut microbiome. METHODS AND RESULTS: Thirty-six C57BL/6 male mice are randomly assigned to either a normal chow diet containing 1.9% w/w lard or an HFD containing 20.68% w/w lard or 20.68% w/w sea buckthorn pulp oil for 16 weeks. The study finds that POA significantly attenuated hyperlipidemia, insulin resistance, and inflammation in HFD-fed mice. POA supplementation significantly alters the composition of serum metabolites, particularly lipid metabolites in the glycerophospholipid metabolism pathway. POA obviously increases the abundance of Bifidobacterium and decreases the abundance of Allobaculum. Importantly, the study finds that glycerophosphocholine mediates the effect of Bifidobacterium on LDL-C, sphingomyelin mediates the effect of Bifidobacterium on IL-6, and maslinic acid mediates the effect of Allobaculum on IL-6. CONCLUSION: The results suggest that exogenous POA can improve metabolic disorders and inflammation in HFD-fed mice, potentially by modulating the serum metabolome and gut microbiome.

Wallace melon juice fermented with Lactobacillus alleviates dextran sulfate sodium-induced ulcerative colitis in mice through modulating gut microbiota and the metabolism.

Fermented foods have shown promise in preventing or treating ulcerative colitis (UC) via regulating intestinal flora and correcting metabolic disorders. However, the prevention effect of fermented Wallace melon juice (FMJ) on UC is unclear. In this study, the effects of FMJ on dextran sodium sulfate (DSS)-induced UC were investigated via 16S rRNA sequencing and non-targeted metabolomics. The results showed that FMJ was effective in alleviating the symptoms of UC, reducing histological damage and oxidative stress, decreasing the levels of pro-inflammatory cytokines. After FMJ treatment, the level of propionic acid, butyric acid, and valeric acid increased by 14.1%, 44.4%, and 52.4% compared to DSS-induced UC mice. Meanwhile, the levels of harmful bacteria such as Oscillospira, Bacteroidetes, and Erysipelotrichaceae and Clostridium decreased, while the levels of beneficial bacteria such as Akkermansia, Lactobacillus, and Bifidobacterium increased. Fecal metabolomics analysis identified 31 differential metabolites, which could regulate metabolic disorders in UC mice by controlling the primary bile acid biosynthesis, purine metabolism, and pantothenate and CoA biosynthesis pathway. Additionally, the abundances of butyric acid, bile acids, and pantothenic acid were positively correlated with Allobaculum, Bifidobacterium, and other beneficial bacteria (R2 > 0.80, p < 0.01). The results indicated that FMJ played a role in regulating the structure of intestinal flora, which in turn helped in repairing metabolic disorders and alleviated colitis inflammation.

Gut microbiota-based discriminative model for patients with ulcerative colitis: A meta-analysis and real-world study.

Gut microbiota directly interacts with intestinal epithelium and is a significant factor in the pathogenesis of ulcerative colitis (UC). A meta-analysis was performed to investigate gut microbiota composition of patients with UC in the United States. We also collected fecal samples from Chinese patients with UC and healthy individuals. Gut microbiota was tested using 16S ribosomal RNA gene sequencing. Meta-analysis and 16S ribosomal RNA sequencing revealed significant differences in gut bacterial composition between UC patients and healthy subjects. The Chinese UC group had the highest scores for Firmicutes, Clostridia, Clostridiales, Streptococcaceae, and Blautia, while healthy cohort had the highest scores for P-Bacteroidetes, Bacteroidia, Bacteroidales, Prevotellaceae, and Prevotella_9. A gut microbiota-based discriminative model trained on an American cohort achieved a discrimination efficiency of 0.928 when applied to identify the Chinese UC cohort, resulting in a discrimination efficiency of 0.759. Additionally, a differentiation model was created based on gut microbiota of a Chinese cohort, resulting in an area under the receiver operating characteristic curve of 0.998. Next, we applied the model established for the Chinese UC cohort to analyze the American cohort. Our findings suggest that the diagnostic efficiency ranged from 0.8794 to 0.9497. Furthermore, a combined analysis using data from both the Chinese and US cohorts resulted in a model with a diagnostic efficacy of 0.896. In summary, we found significant differences in gut bacteria between UC individuals and healthy subjects. Notably, the model from the Chinese cohort performed better at diagnosing UC patients compared to healthy subjects. These results highlight the promise of personalized and region-specific approaches using gut microbiota data for UC diagnosis.

Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

Excess fermentation and lactic acidosis as detrimental functions of the gut microbes in treatment-naive TB patients.

Introduction: The link between gut microbiota and host immunity motivated numerous studies of the gut microbiome in tuberculosis (TB) patients. However, these studies did not explore the metabolic capacity of the gut community, which is a key axis of impact on the host's immunity. Methods: We used deep sequencing of fecal samples from 23 treatment-naive TB patients and 48 healthy donors to reconstruct the gut microbiome's metabolic capacity and strain/species-level content. Results: We show that the systematic depletion of the commensal flora of the large intestine, Bacteroidetes, and an increase in Actinobacteria, Firmicutes, and Proteobacteria such as Streptococcaceae, Erysipelotrichaceae, Lachnospiraceae, and Enterobacteriaceae explains the strong taxonomic divergence of the gut community in TB patients. The cumulative expansion of diverse disease-associated pathobionts in patients reached 1/4 of the total gut microbiota, suggesting a heavy toll on host immunity along with MTB infection. Reconstruction of metabolic pathways showed that the microbial community in patients shifted toward rapid growth using glycolysis and excess fermentation to produce acetate and lactate. Higher glucose availability in the intestine likely drives fermentation to lactate and growth, causing acidosis and endotoxemia. Discussion: Excessive fermentation and lactic acidosis likely characterize TB patients' disturbed gut microbiomes. Since lactic acidosis strongly suppresses the normal gut flora, directly interferes with macrophage function, and is linked to mortality in TB patients, our findings highlight gut lactate acidosis as a novel research focus. If confirmed, gut acidosis may be a novel potential host-directed treatment target to augment traditional TB treatment.

Causal effects of gut microbiota on autism spectrum disorder: A two-sample mendelian randomization study.

There is increasing evidence that alterations in gut microbiota (GM) composition are associated with autism spectrum disorder (ASD), but no reliable causal relationship has been established. Therefore, a 2-sample Mendelian randomization (MR) study was conducted to reveal a potential causal relationship between GM and ASD. Instrumental variables for 211 GM taxa were obtained from genome-wide association studies (GWAS) and Mendelian randomization studies to estimate their impact on ASD risk in the iPSYCH-PGC GWAS dataset (18,382 ASD cases and 27,969 controls). Inverse variance weighted (IVW) is the primary method for causality analysis, and several sensitivity analyses validate MR results. Among 211 GM taxa, IVW results confirmed that Tenericutes (P value = .0369), Mollicutes (P value = .0369), Negativicutes (P value = .0374), Bifidobacteriales (P value = .0389), Selenomonadales (P value = .0374), Bifidobacteriaceae (P value = .0389), Family XIII (P value = .0149), Prevotella7 (P value = .0215), Ruminococcaceae NK4A214 group (P value = .0205) were potential protective factors for ASD. Eisenbergiella (P value = .0159) was a possible risk factor for ASD. No evidence of heterogeneous, pleiotropic, or outlier single-nucleotide polymorphism was detected. Additionally, further sensitivity analysis verified the robustness of the above results. We confirm a potential causal relationship between certain gut microbes and ASD, providing new insights into how gut microbes mediate ASD. The association between them needs to be further explored and will provide new ideas for the prevention and treatment of ASD.

Causal relationship between the gut microbiota and insomnia: a two-sample Mendelian randomization study.

Background: Changes in the gut microbiota are closely related to insomnia, but the causal relationship between them is not yet clear. Objective: To clarify the relationship between the gut microbiota and insomnia and provide genetic evidence for them, we conducted a two-sample Mendelian randomization study. Methods: We used a Mendelian randomized two-way validation method to discuss the causal relationship. First, we downloaded the data of 462,341 participants relating to insomnia, and the data of 18,340 participants relating to the gut microbiota from a genome-wide association study (GWAS). Then, we used two regression models, inverse-variance weighted (IVW) and MR-Egger regression, to evaluate the relationship between exposure factors and outcomes. Finally, we took a reverse MR analysis to assess the possibility of reverse causality. Results: The combined results show 19 gut microbiotas to have a causal relationship with insomnia (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.01, 1.05; p=0.000 for class. Negativicutes; OR: 1.03; 95% CI: 1.01, 1.05; p=0.000 for order.Selenomonadales; OR: 1.01; 95% CI: 1.00, 1.02; p=0.003 for genus.RikenellaceaeRC9gutgroup). The results were consistent with sensitivity analyses for these bacterial traits. In reverse MR analysis, we found no statistical difference between insomnia and these gut microbiotas. Conclusion: This study can provide a new direction for the causal relationship between the gut microbiota (class.Negativicutes, order.Selenomonadales, genus.Lactococcus) and insomnia and the treatment or prevention strategies of insomnia.