IMOVNN: incomplete multi-omics data integration variational neural networks for gut microbiome disease prediction and biomarker identification.

The gut microbiome has been regarded as one of the fundamental determinants regulating human health, and multi-omics data profiling has been increasingly utilized to bolster the deep understanding of this complex system. However, stemming from cost or other constraints, the integration of multi-omics often suffers from incomplete views, which poses a great challenge for the comprehensive analysis. In this work, a novel deep model named Incomplete Multi-Omics Variational Neural Networks (IMOVNN) is proposed for incomplete data integration, disease prediction application and biomarker identification. Benefiting from the information bottleneck and the marginal-to-joint distribution integration mechanism, the IMOVNN can learn the marginal latent representation of each individual omics and the joint latent representation for better disease prediction. Moreover, owing to the feature-selective layer predicated upon the concrete distribution, the model is interpretable and can identify the most relevant features. Experiments on inflammatory bowel disease multi-omics datasets demonstrate that our method outperforms several state-of-the-art methods for disease prediction. In addition, IMOVNN has identified significant biomarkers from multi-omics data sources.

The therapeutic potential of dietary intervention: based on the mechanism of a tryptophan derivative-indole propionic acid on metabolic disorders.

Tryptophan (TRP) contributes to individual immune homeostasis and good condition via three complex metabolism pathways (5-hydroxytryptamine (5-HT), kynurenine (KP), and gut microbiota pathway). Indole propionic acid (IPA), one of the TRP derivatives of the microbiota pathway, has raised more attention because of its impact on metabolic disorders. Here, we retrospect increasing evidence that TRP metabolites/IPA derived from its proteolysis impact host health and disease. IPA can activate the immune system through aryl hydrocarbon receptor (AHR) and/or Pregnane X receptor (PXR) as a vital mediator among diet-caused host and microbe cross-talk. Different levels of IPA in systemic circulation can predict the risk of NAFLD, T2DM, and CVD. IPA is suggested to alleviate cognitive impairment from oxidative damage, reduce gut inflammation, inhibit lipid accumulation and attenuate the symptoms of NAFLD, putatively enhance the intestinal epithelial barrier, and maintain intestinal homeostasis. Now, we provide a general description of the relationships between IPA and various physiological and pathological processes, which support an opportunity for diet intervention for metabolic diseases.

Bifidobacterium longum subsp. infantis as widespread bacteriocin gene clusters carrier stands out among the Bifidobacterium.

Bifidobacterium is the dominant genus, particularly in the intestinal tract niche of healthy breast-fed infants, and many of these strains have been proven to elicit positive effects on infant development. In addition to its effective antimicrobial activity against detrimental microorganisms, it helps to improve the intestinal microbiota balance. The isolation and identification of bacteriocins from Bifidobacterium have been limited since the mid-1980s, leading to an underestimation of its ability for bacteriocin production. Here, we employed a silicon-based search strategy to mine 354 putative bacteriocin gene clusters (BGCs), most of which have never been reported, from the genomes of 759 Bifidobacterium strains distributed across 9 species. Consistent with previous reports, most Bifidobacterium strains did not carry or carry only a single BGC; however, Bifidobacterium longum subsp. infantis, in contrast to other Bifidobacterium species, carried numerous BGCs, including lanthipeptides, lasso peptides, thiopeptides, and class IId bacteriocins. The antimicrobial activity of the crude bacteriocins and transcription analysis confirmed its potential for bacteriocin biosynthesis. Additionally, we investigated the association of bacteriocins with the phylogenetic positions of their homologs from other genera and niches. In conclusion, this study re-examines a few Bifidobacterium species traditionally regarded as a poor source of bacteriocins. These bacteriocin genes impart a competitive advantage to Bifidobacterium in colonizing the infant intestinal tract. IMPORTANCE Development of the human gut microbiota commences from birth, with bifidobacteria being among the first colonizers of the newborn intestinal tract and dominating it for a considerable period. To date, the genetic basis for the successful adaptation of bifidobacteria to this particular niche remains unclear since studies have mainly focused on glycoside hydrolase and adhesion-related genes. Bacteriocins are competitive factors that help producers maintain colonization advantages without destroying the niche balance; however, they have rarely been reported in Bifidobacterium. The advancement in sequencing methods and bacteriocin databases enables the use of a silicon-based search strategy for the comprehensive and rapid re-evaluation of the bacteriocin distribution of Bifidobacterium. Our study revealed that B. infantis carries abundant bacteriocin biosynthetic gene clusters for the first time, presenting new evidence regarding the competitive interactions of Bifidobacterium in the infant intestinal tract.

Diversity within the species Clostridium butyricum: pan-genome, phylogeny, prophage, carbohydrate utilization, and antibiotic resistance.

AIMS: Clostridium butyricum has been recognized as a strong candidate for the "next generation of probiotics" due to its beneficial roles on humans. Owing to our current understanding of this species is limited, it is imperative to unveil the genetic variety and biological properties of C. butyricum on sufficient strains. METHODS AND RESULTS: We isolated 53 C. butyricum strains and collected 25 publicly available genomes to comprehensively assess the genomic and phenotypic diversity of this species. Average nucleotide identity and phylogeny suggested that multiple C. butyricum strains might share the same niche. Clostridium butyricum genomes were replete with prophage elements, but the CRISPR-positive strain efficiently inhibited prophage integration. Clostridium butyricum utilizes cellulose, alginate, and soluble starch universally, and shows general resistance to aminoglycoside antibiotics. CONCLUSIONS: Clostridium butyricum exhibited a broad genetic diversity from the extraordinarily open pan-genome, extremely convergent core genome, and ubiquitous prophages. In carbohydrate utilization and antibiotic resistance, partial genotypes have a certain guiding significance for phenotypes.

Broccoli seed extract rich in polysaccharides and glucoraphanin ameliorates DSS-induced colitis via intestinal barrier protection and gut microbiota modulation in mice.

BACKGROUND: Broccoli has received widespread attention because of its anti-inflammatory and antioxidant effects. The present study aimed to explore the composition of broccoli seed extract (BSE) and its effect on colitis induced by dextran sulfate sodium (DSS). RESULTS: BSE mainly comprises glucoraphanin and polysaccharides composed of arabinose, galactose, glucose and mannose. Animal experiments suggested that BSE intervention effectively reversed body weight loss, suppressed the levels of proinflammatory interleukin-6, tumor necrosis factor-α and interleukin-1ß, and elevated the levels of anti-inflammatory interleukin-10 and the activities of superoxide dismutase and glutathione in DSS-induced colitis mice. According to histopathologic and immunohistochemical analysis of colon tissue, BSE intervention may repair the intestinal barrier by upregulating mRNA levels and the expression of tight junction proteins (claudin-1, occludin and zonula occludens-1). Gas chromatography-mass spectrometry (MS) analysis demonstrated that cecal short-chain fatty acids in mice with BSE administration were significantly increased compared with the model group. Sulforaphane and sulforaphane-N-acetylcysteine were only detected in BSE group mice by ultra-performance liquid chromatography-MS analysis. In addition, BSE intervention evidently increased the abundance of Alistipeds, Coriobacteriaceae UCG-002 and Bifidobacterium and decreased the abundance of Escheichia-Shinella, Lachnospiraceae others, Parabacteroides, Ruminococcaceae others and Turicibacter, which possibly promoted carbohydrate metabolism and short-chain fatty acid production. CONCLUSION: The present study aimed to elucidate the effect of BSE on colitis and found that BSE, as a novel food ingredient, has great potential for the improvement of colitis. © 2022 Society of Chemical Industry.

Population genomics of Lacticaseibacillus paracasei: pan-genome, integrated prophage, antibiotic resistance, and carbohydrate utilization.

Lacticaseibacillus paracasei has beneficial effects on human health and holds promising potential as a probiotic for use in the development of functional foods, especially dairy products. This species can adapt to a variety of ecological niches and presents fundamental carbohydrate metabolism and tolerance to environmental stresses. However, the population structure, ecology, and antibiotic resistance of Lc. paracasei in diverse ecological niches are poorly understood. Reclassification of Lc. paracasei as a separate species of Lacticaseibacillus has stimulated renewed interest in its research, and a deeper interpretation of it will be important for screening strains beneficial to human health. Here, we collected 121 self-isolated and 268 publicly available Lc. paracasei genomes discussed how genomic approaches have advanced our understanding of its taxonomy, ecology, evolution, diversity, integrated prophage-related element distribution, antibiotic resistance, and carbohydrate utilization. Moreover, for the Lc. paracasei strains isolated in this study, we assessed the inducibility of integrated prophages in their genomes and determined the phenotypes that presented tolerance to multiple antibiotics to provide evidence for safety evaluations of Lc. paracasei during the fermentation processes.

Oral microbiome characteristics in children with and without early childhood caries.

OBJECTIVE: Early childhood caries (ECC) negatively affects children's growth due to its close relation to an imbalance of the oral microbiota. This study aimed to evaluate the distribution of the oral microbiota in children with ECC and healthy individuals. METHODS: The oral microbiota of 20 children with dental caries from both carious teeth (CC cohort) and healthy teeth (CH cohort), and the oral microbiota of 20 healthy control children (HH cohort) were subjected to 16S rDNA sequencing. RESULTS: The results revealed significant differences between the microbial structure of the CC and CH cohorts of every child with ECC. The most common microbes were Streptococcus, Neisseria, Leptotrichia, Lautropia and Haemophilus. Specifically, the CC cohort contained Lactobacillus, Veillonella, and Prevotella 7, the CH cohort contained Actinomyces, Bifidobacterium and Abiotrophia, and the HH cohort mainly contained Neisseria, Leptotrichia, Porphyromonas and Gemella. Lastly, we established a random forest model consisting of 10 genera (Prevotella 7, Actinobacillus, etc.) which demonstrated promising clinical diagnostic ability (area under the curve (AUC) = 89.8%). These findings indicate that oral microbiota can potentially be used as therapeutic targets or diagnostic markers for the early prediction and prevention of caries in children.

Machine learning framework for gut microbiome biomarkers discovery and modulation analysis in large-scale obese population.

BACKGROUND: The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations and perform precisely targeted modulation for obese individuals. RESULTS: This study proposed a systematic machine learning framework and applied it to 870 human stool metagenomes across five countries to obtain comprehensive regional shared biomarkers and conduct a personalized modulation analysis. In our pipeline, a heterogeneous ensemble feature selection diagram is first developed to determine an optimal subset of biomarkers through the aggregation of multiple techniques. Subsequently, a deep reinforcement learning method was established to alter the targeted composition to the desired healthy target. In this manner, we can realize personalized modulation by counterfactual inference. Consequently, a total of 42 species were identified as regional shared biomarkers, and they showed good performance in distinguishing obese people from the healthy group (area under curve (AUC) =0.85) when demonstrated on validation datasets. In addition, by pooling all counterfactual explanations, we found that Akkermansia muciniphila, Faecalibacterium prausnitzii, Prevotella copri, Bacteroides dorei, Bacteroides eggerthii, Alistipes finegoldii, Alistipes shahii, Eubacterium sp. _CAG_180, and Roseburia hominis may be potential broad-spectrum targets with consistent modulation in the multi-regional obese population. CONCLUSIONS: This article shows that based on our proposed machine-learning framework, we can obtain more comprehensive and accurate biomarkers and provide modulation analysis for the obese population. Moreover, our machine-learning framework will also be very useful for other researchers to further obtain biomarkers and perform counterfactual modulation analysis in different diseases.

A multiphase dietetic protocol incorporating an improved ketogenic diet enhances weight loss and alters the gut microbiome of obese people.

The prevalence of obesity and its associated diseases is increasing. In the current study, 15 obese subjects took part in a 12-week multiphase dietetic protocol incorporating an improved ketogenic diet (MDP-i-KD) (KYLLKS 201806). We investigated the effects of the MDP-i-KD on the anthropometric parameters and the gut microbiota of obese subjects. Our results showed that the MDP-i-KD led to significant reductions in body mass index in obese subjects. The MDP-i-KD significantly decreased the relative abundance of the Lachnospiraceae_ND3007_group, the Eubacterium_hallii_group, and Pseudomonas and Blautia. In addition, gut microbiota co-occurrence networks in obese subjects were restructured to a more healthy condition after weight loss. These results show that the MDP-i-KD enhanced weight loss, which may be associated with dietary-induced changes in the gut microbiome. Our results emphasise the importance of determining the interaction between the host and microbial cells to comprehensively understand the mechanism by which diet affects host physiology and the microbiota.

Limosilactobacillus reuteri Attenuates Atopic Dermatitis via Changes in Gut Bacteria and Indole Derivatives from Tryptophan Metabolism.

Gut bacteria are closely associated with the development of atopic dermatitis (AD) due to their immunoregulatory function. Indole derivatives, produced by gut bacteria metabolizing tryptophan, are ligands to activate the aryl hydrocarbon receptor (AHR), which plays a critical role in attenuating AD symptoms. Limosilactobacillus reuteri, a producer of indole derivatives, regulates mucosal immunity via activating the AHR signaling pathway. However, the effective substance and mechanism of L. reuteri in the amelioration of AD remain to be elucidated. In this research, we found that L. reuteri DYNDL22M62 significantly improved AD-like symptoms in mice by suppressing IgE levels and the expressions of thymic stromal lymphopoietin (TSLP), IL-4, and IL-5. L. reuteri DYNDL22M62 induced an increase in the production of indole lactic acid (ILA) and indole propionic acid (IPA) via targeted tryptophan metabolic analysis and the expression of AHR in mice. Furthermore, L. reuteri DYNDL22M62 increased the proportions of Romboutsia and Ruminococcaceae NK4A214 group, which were positively related to ILA, but decreased Dubosiella, which was negatively related to IPA. Collectively, L. reuteri DYNDL22M62 with the role of modulating gut bacteria and the production of indole derivatives may attenuate AD via activating AHR in mice.

Evaluation of the Potential Protective Effects of Lactobacillus Strains against Helicobacter pylori Infection: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: The beneficial effects of probiotic supplementation standard antibiotic therapies for Helicobacter pylori infection have been verified, but the ability of probiotic monotherapy to eradicate H. pylori remains unclear. Aim: To evaluate the accuracy and efficacy of specific Lactobacillus strains against H. pylori infection. Methods: Seventy-eight patients with H. pylori infection were treated with strain L. crispatus G14-5M (L. crispatus CCFM1118) or L. helveticus M2-09-R02-S146 (L. helveticus CCFM1121) or L. plantarum CCFM8610 at a dose of 2 g twice daily for one month. 14C-urea breath test, the gastrointestinal symptom rating scale, serum pepsinogen concentrations, and serum cytokine concentrations of patients were measured at baseline and end-of-trial to analyze the effect of the Lactobacillus strains in eradicating H. pylori infection and reducing gastrointestinal discomfort in patients. In addition, the composition and abundance of the intestinal microbiota of patients were also measured at end-of-trial. Results: The 14C-urea breath test value of the three Lactobacillus treatment groups had decreased significantly, and the eradication rate of H. pylori had increased by the end of the trial. In particular, the eradication rate in the G14-5M treatment group was significantly higher than the placebo group (70.59% vs. 15.38%, P=0.0039), indicating that one-month administration of the G14-5M regimen was sufficient to eradicate H. pylori infection. The ingestion of Lactobacillus strains also ameliorated the gastrointestinal symptom rating scale scores, and the serum interleukin-8 concentrations of H. pylori-infected patients appeared to modulate the gut microbiota of patients. However, none of the Lactobacillus strains had a significant effect on general blood physiological characteristics, serum tumor necrosis factor α concentrations, or serum pepsinogen concentrations in the patients. Conclusion: Three Lactobacillus strains significantly alleviate the gastrointestinal discomfort and the gastric inflammatory response of H. pylori-infected patients. The activity of probiotics in eradicating H. pyloriinfection may be species/strain specific.

Promotion mechanism of self-transmissible degradative plasmid transfer in maize rhizosphere and its application in naphthalene degradation in soil.

Rhizospheres can promote self-transmissible plasmid transfer, however, the corresponding mechanism has not received much attention. Plant-microbe remediation is an effective way to promote pollutant biodegradation; however, some pollutants, such as naphthalene, are harmful to plants and result in inefficient plant-microbe remediation. In this study, transfer of a TOL-like plasmid, a self-transmissible plasmid loaded with genetic determinants for pollutant degradation, among different bacteria was examined in bulk and rhizosphere soils as well as addition of maize root exudate and its artificial root exudate (ARE). The results showed that the numbers of transconjugants and recipients as well as bacterial metabolic activities, such as xylE mRNA expression levels and catechol 2,3-dioxygenase (C23O) activities of bacteria, remained high in rhizosphere soils, when compared with bulk soils. The number of transconjugants and bacterial metabolic activities increased with the increasing exudate and ARE concentrations, whereas the populations of donor and recipient bacteria were substantially unaltered at all concentrations. All the experiments consistently showed that a certain number of bacteria is required for self-transmissible plasmid transfer, and that the increased plasmid transfer might predominantly be owing to bacterial metabolic activity stimulated by root exudates and ARE. Furthermore, ARE addition increased naphthalene degradation by transconjugants in both culture medium and soil. Thus, the combined action of a wide variety of components in ARE might contribute to the increased plasmid transfer and naphthalene degradation. These findings suggest that ARE could be an effectively alternative for plant-microbe remediation of pollutants in environments where plants cannot survive.

The role of phenylalanine hydroxylase in lipogenesis in the oleaginous fungus Mortierella alpina.

Phenylalanine hydroxylase (PAH) catalyses the irreversible hydroxylation of phenylalanine to tyrosine, which is the rate-limiting reaction in phenylalanine metabolism in animals. A variety of polyunsaturated fatty acids can be synthesized by the lipid-producing fungus Mortierella alpina, which has a wide range of industrial applications in the production of arachidonic acid. In this study, RNA interference (RNAi) with the gene PAH was used to explore the role of phenylalanine hydroxylation in lipid biosynthesis in M. alpina. Our results indicated that PAH knockdown decreased the PAH transcript level by approximately 55% and attenuated cellular fatty acid biosynthesis. Furthermore, the level of NADPH, which is a critical reducing agent and the limiting factor in lipogenesis, was decreased in response to PAH RNAi, in addition to the downregulated transcription of other genes involved in NADPH production. Our study indicates that PAH is part of an overall enzymatic and regulatory mechanism supplying NADPH required for lipogenesis in M. alpina.

Community-wide changes reflecting bacterial interspecific interactions in multispecies biofilms.

Existence of most bacterial species, in natural, industrial, and clinical settings in the form of surface-adhered communities or biofilms has been well acknowledged for decades. Research predominantly focusses on single-species biofilms as these are relatively easy to study. However, microbiologists are now interested in studying multispecies biofilms and revealing interspecific interactions in these communities because of the existence of a plethora of different bacterial species together in almost all natural settings. Multispecies biofilms-led emergent properties are triggered by bacterial social interactions which have huge implication for research and practical knowledge useful for the control and manipulation of these microbial communities. Here, we discuss some important bacterial interactions that take place in multispecies biofilm communities and provide insights into community-wide changes that indicate bacterial interactions and elucidate underlying mechanisms.

The diversity of gut microbiota in type 2 diabetes with or without cognitive impairment.

BACKGROUND: Diabetes is associated with a high risk of developing cognitive impairment, but the underlying mechanism remains unclear. Recent studies have found that gut microbiota may be involved in the progression of diabetes-associated cognitive impairment. AIMS: To analyze the diversity of gut microbiota in type 2 diabetes with or without cognitive impairment METHODS: 16S rRNA sequencing was used to detect the gut microbiota composition in 154 type 2 diabetes (T2DM) subjects RESULTS: Among 154 elderly T2DM participants included in our study, 73 with normal and 81 with impaired cognition. Lower levels of hemoglobin and HDL were observed in subjects with cognitive impairment. Patients with cognitive impairment had a lower abundance of Tenericutes. Comparison at the genus level revealed that T2DM patients with cognitive impairment had a decreased abundance of Bifidobacterium and unranked-RF39 and an increased abundance of Peptococcus and unranked-Leuconostocaceae. Additionally, the relative abundance of Veillonella and Pediococcus were decreased in subjects with cognitive impairment. Furthermore, the relative abundance of 7 sub-functions was significantly changed in the group with cognitive impairment. Calcium signaling pathways and the Renin-angiotensin system were upregulated in the cognitive impairment group while GnRH signaling, Fc gamma R-mediated phagocytosis, endocytosis, isoflavonoid biosynthesis, and cytochrome P450 were deregulated. CONCLUSION: Bifidobacterium may be associated with cognition in T2DM. Calcium signaling and renin-angiotensin system were shown to be associated with diabetes-associated cognitive impairment through gut microbiota.

Integration of Transcriptome and Metabolome Reveals the Genes and Metabolites Involved in Bifidobacterium bifidum Biofilm Formation.

Bifidobacterium bifidum strains, an important component of probiotic foods, can form biofilms on abiotic surfaces, leading to increased self-resistance. However, little is known about the molecular mechanism of B. bifidum biofilm formation. A time series transcriptome sequencing and untargeted metabolomics analysis of both B. bifidum biofilm and planktonic cells was performed to identify key genes and metabolites involved in biofilm formation. Two hundred thirty-five nonredundant differentially expressed genes (DEGs) (including vanY, pstS, degP, groS, infC, groL, yajC, tadB and sigA) and 219 nonredundant differentially expressed metabolites (including L-threonine, L-cystine, L-tyrosine, ascorbic acid, niacinamide, butyric acid and sphinganine) were identified. Thirteen pathways were identified during the integration of both transcriptomics and metabolomics data, including ABC transporters; quorum sensing; two-component system; oxidative phosphorylation; cysteine and methionine metabolism; glutathione metabolism; glycine, serine and threonine metabolism; and valine, leucine and isoleucine biosynthesis. The DEGs that relate to the integration pathways included asd, atpB, degP, folC, ilvE, metC, pheA, pstS, pyrE, serB, ulaE, yajC and zwf. The differentially accumulated metabolites included L-cystine, L-serine, L-threonine, L-tyrosine, methylmalonate, monodehydroascorbate, nicotinamide, orthophosphate, spermine and tocopherol. These results indicate that quorum sensing, two-component system and amino acid metabolism are essential during B. bifidum biofilm formation.

Both living and dead Faecalibacterium prausnitzii alleviate house dust mite-induced allergic asthma through the modulation of gut microbiota and short-chain fatty acid production.

BACKGROUND: Asthma is increasingly prevalent worldwide, and novel strategies to prevent or treat this disease are needed. Probiotic intervention has recently been reported to be effective for asthma prevention. Here, we explored the effects of Faecalibacterium prausnitzii on the development of allergic airway inflammation in a murine model of house dust mite (HDM)-induced allergic asthma. RESULTS: Supplementation with living and dead F. prausnitzii blocked eosinophil, neutrophil, lymphocyte and macrophage influx and alleviated the pathological changes. Moreover, both living and dead F. prausnitzii administration decreased the levels of interleukin (IL)-4, IL-5, IL-13 and immunoglobulin G1, elevated regulatory T cell (Tregs) ratio, improved microbial dysbiosis and enhanced short-chain fatty acid (SCFA) production. Network correlation analysis revealed that the immune indicators were strongly associated with SCFA production. Based on the linear discriminant analysis effect size, Turicibacter was found to be the core genus related to HDM-induced asthma. Living F. prausnitzii treatment enriched Faecalibaculum, Dubosiella and Streptococcus, while dead F. prausnitzii treatment increased Muribaculaceae and Parabacteroides. Interestingly, both living and dead F. prausnitzii administration enriched Lachnoclostridium and normalized the pathways involving carbohydrate and lipid metabolism, which might be related to SCFA production. CONCLUSION: Faecalibacterium prausnitzii exerts an anti-asthmatic effect partly by gut microbiota modulation and SCFA production, suggesting its potential as a probiotic agent for allergic asthma prevention. © 2021 Society of Chemical Industry.

The role of MTHFDL in mediating intracellular lipogenesis in oleaginous Mortierella alpina.

The oleaginous fungus Mortierella alpina can synthesize a variety of polyunsaturated fatty acids, which are used extensively in industry for the production of arachidonic acid (AA). NADPH is the limiting factor and critical reducing agent in lipid biosynthesis. In the folate cycle, methylenetetrahydrofolate dehydrogenase (MTHFDL) catalyzes the conversion of methylene tetrahydrofolate into 10-formyl-tetrahydrofolate with the reduction of NADP+ to NADPH. MTHFDL RNAi was used to investigate the role of the folate cycle in lipogenesis. Gene knockdown decreased the transcript levels of MTHFDL by about 50 % and attenuated cell fatty acid synthesis. The observation of decreased NADPH levels and downregulated NADPH-producing genes in response to MTHFDL RNAi indicates a novel aspect of the NADPH regulatory mechanism. Thus, our study demonstrates that MTHFDL plays key role in the mediation of NADPH in lipogenesis in M. alpina.

Potential of gut microbiome for detection of autism spectrum disorder.

Autism spectrum disorder (ASD) is a neuro developmental disorder characterized by a series of abnormal social behaviors. The increasing prevalence of ASD has led to the discovery of a correlation with the intestinal microbiome in many studies. In our research, we evaluated 297 subjects, including 169 individuals with ASD and 128 neurotypical subjects, from the Sequence Read Archive database. We conducted a series of analyses, including alpha-diversity, phylogenetic profiles, and functional profiles, to explore the correlation between the gut microbiome and ASD. The principal component analysis (PCA) indicated that ASD and neurotypical subjects could be divided based on the unweighted UniFrac distance. The genera Prevotella, Roseburia, Ruminococcus, Megasphaera, and Catenibacterium might be biomarkers of ASD after linear discriminant analysis effect size (LEfSe) evaluation and Random Forest analysis, respectively. The functional analysis found six significant pathways between ASD and neurotypical subjects, including oxidative phosphorylation, nucleotide excision repair, peptidoglycan biosynthesis, photosynthesis, photosynthesis proteins, and two-component system. Based on these alterations of the intestinal microbiome in ASD subjects, we developed four machine learning models: random forest (RF), Multilayer Perceptron (MLP), kernelized support vector machines with the RBF kernel (SVMs), and Decision trees (DT). Notably, the RF model after RF selection was superior, with an F1 score of 0.74 and area under the curve of 0.827(0.004), suggesting the reliability and generalizability of predictive model. Besides, the validation performance of RF model after RF selection could be 0.75(0.01) on external cohort collected by our laboratory. Our study advances the understanding of human gut microbiome in ASD that designing and evaluating microbially based interventions of ASD.

Probiotics modulate the gut microbiota composition and immune responses in patients with atopic dermatitis: a pilot study.

PURPOSE: Many studies have investigated the association between intestinal barrier impairment and the onset of atopic dermatitis (AD). The gut microbiota is essential to maintain physiological homeostasis and immune regulation of host. Therefore, the objectives were to determine the effects of probiotics on the clinical symptoms, immune responses, and gut microbiota in AD patients. METHODS: 109 patients were randomly divided into 4 groups, including placebo group, oligosaccharides group, Bifidobacterium bifidum CCFM16 group, and Lactobacillus plantarum CCFM8610 group. At the end of the experiment, serological indicators, SCORAD, and DLQI indices were assessed. V3-V4 region of the 16S ribosomal RNA gene was sequenced to evaluate changes in the gut microbiota. Linear discriminant analysis (LDA) effect size was used to uncover microbial biomarkers and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used to predict gene family abundances based on 16S information. RESULTS: The results demonstrated that CCFM8610 significantly decreased the SCORAD index, and increased the serum IL-10 levels. Supplement with CCFM8610 and CCFM16 significantly influenced the alpha diversity, increased the proportion of Bacteroidetes, and reduced the F/B ratio. CCFM8610 treatment downregulated the functional genes of gut microbiota involving Staphylococcus aureus infection and upregulated the steroid hormone biosynthesis. CONCLUSION: The results indicated a positive correlation between decreased SCORAD index and CCFM8610 treatment, and that CCFM8610 regulated the immune responses in AD patients. CCFM8610 treatment influences the gut microbiota composition and functional changes. In conclusion, L. plantarum CCFM8610 exerts the strain-specific amelioration effects on patients with AD. TRIAL REGISTRATION: ChiCTR1800015330 (Clinicaltrials.gov Identifier).