The alleviative effects of viable and inactive Lactobacillus paracasei CCFM1120 against alcoholic liver disease via modulation of gut microbiota and the Nrf2/HO-1 and TLR4/MyD88/NF-κB pathways.

Probiotics can alleviate alcoholic liver disease. However, whether inactive counterparts can produce similar outcomes requires further investigation. We investigated the effects of viable (V) and dead (D) Lactobacillus paracasei CCFM1120 on alcohol-induced ALD mice. The results showed that CCFM1120V and D ameliorated the disease symptoms and intestinal injury. Specifically, these interventions strengthened the intestinal barrier, as evidenced by the increased expression of ZO-1 (zonula occludens 1), occludin, and claudin-1 in the colon and the restored ileal microstructure, including the villi and crypts. In addition, they enhanced the antioxidant capacity of the liver by reducing the production of malondialdehyde and increasing the levels of glutathione and superoxide dismutase. The activation of Nrf2 and HO-1 may be responsible for recovering the antioxidant capacity. Interventions can decrease mouse TNF-α, IL-6 and IL-1ß content in serum, probably through the TLR4/MyD88/NF-κB pathway. Furthermore, they possess the ability to restore the quantities of bacteria responsible for producing butyric acid, such as Lactobacillus, Blautia, Bifidobacterium, Ruminococcaceae, Faecalibaculum and Lachnospiraceae. Taken together, CCFM1120V and D apparently can modify the composition of the gut microbiota, foster the gastrointestinal equilibrium, fortify the intestinal barrier, augment the antioxidant capacity of the liver, and effectively shield it from ethanol-induced injury.

Bifidobacterium animalis subsp. lactis CCFM1274 relieved allergic asthma symptoms by modifying intestinal tryptophan metabolism in mice.

Approximately two-thirds of patients with asthma, a common inflammatory airway disease, are thought to present with allergies. Probiotics and tryptophan metabolites are becoming increasingly important in treating allergic asthma. This study aimed to identify potential probiotic strains and tryptophan metabolites that could alleviate asthma symptoms. Based on in vitro fermentation experiments, we evaluated variations in probiotic capacity to metabolize tryptophan. Of the eight tested strains, Bifidobacterium animalis subsp. lactis CCFM1274 produced relatively high levels of indole-3-carboxaldehyde (I3C). A mouse model of allergic asthma was established by oral administration of ovalbumin (OVA) and was subjected to oral administration of probiotics. The results demonstrated that treatment with CCFM1274 reduced the tendency for body weight loss and mortality in OVA-induced asthmatic mice. Ingestion of CCFM1274 improved the infiltration of perivascular and peribronchial inflammatory cells in the lung sections stained with hematoxylin and eosin (H&E). This outcome was accompanied by a reduction in the serum levels of OVA-specific immunoglobulin E (OVA-sIgE) and in the levels of IL-10 and IL-17 in the bronchoalveolar lavage fluid (BALF). The linear discriminant analysis effect size (LEfSe) of the gut microbiota showed that CCFM1274 increased the relative abundance of Bifidobacterium. In conclusion, CCFM1274 remodeled intestinal tryptophan metabolism in mice and contributed to the improvement of allergic asthma.

Construction and characterization of stable multi-species biofilms formed by nine core gut bacteria on wheat fiber.

Microbial aggregation mainly occurs on the intestinal epithelium, mucosal layer and undigested food particles in the gastrointestinal tract (GIT). Undigested food particles are usually insoluble dietary fiber (IDF), which can be easily obtained through daily diet, but there are few studies investigating whether the gut bacteria adhering to undigested food particles can form multi-species biofilms. In this study, we prepared mono- and multi-species biofilms using 18 core gut bacteria via a dynamic fermentation method, and it was found that multi-species composed of nine core gut bacteria (M9) showed the best biofilm formation ability. Cell counts of the nine bacteria in multi-species biofilms were 9.36, 11.85, 10.17, 9.93, 12.88, 11.39, 10.089, 9.06, and 13.21 Log10 CFU mL-1. M9 was tightly connected and regularly stacked on wheat fiber and had larger particle sizes than mono-species biofilms. M9 retained biofilm formation ability under pH and bile salt stresses. A human feces invasion experiment demonstrated that M9 can stably adhere to wheat fiber under the interference of complex gut bacteria, and the M9 multi-species biofilm had positions that can be filled by various gut bacteria. Metabolome results indicated that the M9 multi-species biofilm had more metabolic productions and more complex interspecies interactions than mono-species biofilms. This study provides a dynamic fermentation method to prepare multi-species biofilms on wheat fiber in vitro. It will also offer a research basis for clarifying whether gut bacteria can utilize IDF to form biofilm structures in vivo and the possible interspecific interactions and physiological functions of bacteria in biofilms.

Gut Microbiota-Derived Tryptophan Metabolites Alleviate Allergic Asthma Inflammation in Ovalbumin-Induced Mice.

Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis.

Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and ß-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.

Prenatal PFAS exposure, gut microbiota dysbiosis, and neurobehavioral development in childhood.

Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.

Achieving healthy aging through gut microbiota-directed dietary intervention: Focusing on microbial biomarkers and host mechanisms.

BACKGROUND: Population aging has become a primary global public health issue, and the prevention of age-associated diseases and prolonging healthy life expectancies are of particular importance. Gut microbiota has emerged as a novel target in various host physiological disorders including aging. Comprehensive understanding on changes of gut microbiota during aging, in particular gut microbiota characteristics of centenarians, can provide us possibility to achieving healthy aging or intervene pathological aging through gut microbiota-directed strategies. AIM OF REVIEW: This review aims to summarize the characteristics of the gut microbiota associated with aging, explore potential biomarkers of aging and address microbiota-associated mechanisms of host aging focusing on intestinal barrier and immune status. By summarizing the existing effective dietary strategies in aging interventions, the probability of developing a diet targeting the gut microbiota in future is provided. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review is focused on three key notions: Firstly, gut microbiota has become a new target for regulating health status and lifespan, and its changes are closely related to age. Thus, we summarized aging-associated gut microbiota features at the levels of key genus/species and important metabolites through comparing the microbiota differences among centenarians, elderly people and younger people. Secondly, exploring microbiota biomarkers related to aging and discussing future possibility using dietary regime/components targeted to aging-related microbiota biomarkers promote human healthy lifespan. Thirdly, dietary intervention can effectively improve the imbalance of gut microbiota related to aging, such as probiotics, prebiotics, and postbiotics, but their effects vary among.

Mannan-oligosaccharides promote gut microecological recovery after antibiotic disturbance.

Antibiotic treatment often causes collateral damage to the gut microbiota, including changes in its diversity and composition. Dietary fiber helps maintain intestinal health, regulate short-chain fatty acids, and promote the recovery of the intestinal microbiome. However, it is currently unknown which specific plant-based dietary fiber is optimal as a dietary supplement for restoring the intestinal microbiota after antibiotic disturbance. Previously, we proposed predictive recovery-associated bacterial species (p-RABs) and identified the most important interventions. This study aimed to identify an optimal form of dietary fiber to recover the gut microbiome after antibiotic treatment. Therefore, we examined the types of dietary fibers associated with p-RABs through a p-RAB-metabolite bilayer network constructed from prior knowledge; we searched for dietary fiber that could provide nutritional support for Akkermansia muciniphila and Bacteroides uniformis. C57BL/6J mice were fed with 500 mg kg-1 of different types of dietary fibers daily for one week after being treated with ampicillin. The results showed that mannan-oligosaccharides could better promote the diversity of intestinal microbial growth, enhance the recovery of most genera, including Akkermansia and Bacteroides, and inhibit certain pathogenic bacteria, such as Proteus, compared to the other fiber types. Furthermore, mannan-oligosaccharides could regulate the levels of short-chain fatty acids, especially butyric acid. Functional predictions showed that starch metabolism, galactose metabolism, and the metabolism of other carbohydrates played key roles in the early recovery process. In conclusion, mannan-oligosaccharides could enhance the recovery of the intestinal microbiome after antibiotic treatment, offering valuable insights for targeted dietary strategies.

Effects of Varied Sulfamethazine Dosage and Exposure Durations on Offspring Mice.

The development of antibiotics was a turning point in the history of medicine; however, their misuse and overuse have contributed to the current global epidemic of antibiotic resistance. According to epidemiological studies, early antibiotic exposure increases the risk of immunological and metabolic disorders. This study investigated the effects of exposure to different doses of sulfamethazine (SMZ) on offspring mice and compared the effects of exposure to SMZ on offspring mice in prenatal and early postnatal periods and continuous periods. Furthermore, the effects of SMZ exposure on the gut microbiota of offspring mice were analyzed using metagenome. According to the results, continuous exposure to high-dose SMZ caused weight gain in mice. IL-6, IL-17A, and IL-10 levels in the female offspring significantly increased after high-dose SMZ exposure. In addition, there was a significant gender difference in the impact of SMZ exposure on the gut microbiota of offspring: Continuous high-dose SMZ exposure significantly decreased the relative abundance of Ligilactobacillus murinus, Limosilactobacillus reuteri, Lactobacillus johnsonii, and Bifidobacterium pseudolongum (p < 0.05) in female offspring mice; however, these significant changes were not observed in male offspring mice.

Interspecific differences and mechanisms of Lactobacillus-derived anti-inflammatory exopolysaccharides.

Accumulating evidence has revealed the anti-inflammatory properties of Lactobacillus-derived exopolysaccharides (EPSs). However, interspecific differences among these Lactobacillus-derived anti-inflammatory EPSs have not been investigated. Cell experiments showed that Limosilactobacillus fermentum, Lacticaseibacillus rhamnosus, and Lactiplantibacillus plantarum-derived EPSs exhibited excellent anti-inflammatory efficacy in vitro. Subsequently, we used Lactobacillus-derived EPSs to treat colitis in mice. There was no significant difference in EPS's repair of the intestinal barrier from the five Lactobacillus species. However, Ligilactobacillus salivarius-derived EPSs and L. plantarum-derived EPSs more potently reduced proinflammatory cytokines (TNF-α, IL-1ß, IL-6, TNF-γ, and IL-17), increasing IL-10 concentrations in the colon. Lactobacillus-derived EPS moieties from five species regulate intestinal bacteria at the strain level. Immunofluorescence staining revealed that owing to the different infiltration and polarization effects of Lactobacillus-derived EPSs on macrophages, the in vitro and in vivo anti-inflammatory effects of Lactobacillus-derived EPSs were inconsistent. The structure-activity relationship showed that Lactobacillus-derived EPSs with high fructose content had excellent anti-inflammatory activity in vivo. The results mentioned above revealed that the anti-inflammatory activity of Lactobacillus-derived EPSs had interspecific variability, and the mechanism of anti-inflammatory action in vitro and in vivo was different.

A gut aging clock using microbiome multi-view profiles is associated with health and frail risk.

Age-related changes in the microbiome have been reported in previous studies; however, direct evidence for their association with frailty is lacking. Here, we introduce biological age based on gut microbiota (gAge), an integrated prediction model that integrates gut microbiota data from different perspectives with potential background factors for aging assessment. Simulation results show that, compared with a single model, the ensemble model can not only significantly improve the prediction accuracy, but also make full use of the data in unpaired samples. From this, we identified markers associated with age development and grouped markers into accelerated aging and mitigated aging according to their effect on the prediction. Importantly, the application of gAge to an elderly cohort with different frailty levels confirmed that gAge and its predictive residuals are closely related to the individual's health status and frailty stage, and age-related markers overlap significantly with disease and frailty characteristics. Furthermore, we applied the gAge prediction model to another independent cohort of the elderly population for aging assessment and found that gAge could effectively represent the aging population. Overall, our study explains the association between the gut microbiota and frailty, providing potential targets for the development of gut microbiota-based targeted intervention strategies for aging.

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.

Population-level variation in gut bifidobacterial composition and association with geography, age, ethnicity, and staple food.

Bifidobacteria are key gut commensals that confer various health benefits and are commonly used as probiotics. However, little is known about the population-level variation in gut bifidobacterial composition and its affecting factors. Therefore, we analyzed Bifidobacterium species with amplicon sequencing of the groEL gene on fecal samples of 1674 healthy individuals, who belonged to eight ethnic groups and resided in 60 counties/cities of 28 provinces across China. We found that the composition of the bifidobacterial community was associated with geographical factors, demographic characteristics, staple food type, and urbanization. First, geography, which reflects a mixed effect of other variables, explained the largest variation in the bifidobacterial profile. Second, middle adolescence (age 14-17) and age 30 were two key change points in the bifidobacterial community development, and a bifidobacterial community resembling that of adults occurred in middle adolescence, which is much later than the maturation of the whole gut microbial community at approximately age 3. Third, each ethnicity showed a distinct bifidobacterial profile, and the remarkable amount of unknown Bifidobacterium species in the Tibetan gut suggested undiscovered biodiversity. Fourth, wheat as the main staple food promoted the flourish of B. adolescentis and B. longum. Fifth, alpha diversity of the bifidobacterial community decreased with urbanization. Collectively, our findings provide insight into the environmental and host factors that shape the human gut bifidobacterial community, which is fundamental for precision probiotics.

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.

Multi-omics analysis reveals genes and metabolites involved in Bifidobacterium pseudocatenulatum biofilm formation.

Bacterial biofilm is an emerging form of life that involves cell populations living embedded in a self-produced matrix of extracellular polymeric substances (EPS). Currently, little is known about the molecular mechanisms of Bifidobacterium biofilm formation. We used the Bifidobacterium biofilm fermentation system to preparation of biofilms on wheat fibers, and multi-omics analysis of both B. pseudocatenulatum biofilms and planktonic cells were performed to identify genes and metabolites involved in biofilm formation. The average diameter of wheat fibers was around 50 µm, while the diameter of particle in wheat fibers culture of B. pseudocatenulatum was over 260 µm at 22 h with 78.96% biofilm formation rate (BR), and the field emission scanning electron microscopy (FESEM) results showed that biofilm cells on the surface of wheat fibers secreted EPS. Transcriptomic analysis indicated that genes associated with stress response (groS, mntH, nth, pdtaR, pstA, pstC, radA, rbpA, whiB, ybjG), quorum sensing (dppC, livM, luxS, sapF), polysaccharide metabolic process (rfbX, galE, zwf, opcA, glgC, glgP, gtfA) may be involved in biofilm formation. In addition, 17 weighted gene co-expression network analysis (WGCNA) modules were identified and two of them positively correlated to BR. Metabolomic analysis indicated that amino acids and amides; organic acids, alcohols and esters; and sugar (trehalose-6-phosphate, uridine diphosphategalactose, uridine diphosphate-N-acetylglucosamine) were main metabolites during biofilm formation. These results indicate that stress response, quorum sensing (QS), and EPS production are essential during B. pseudocatenulatum biofilm formation.

Weight Loss Promotion in Individuals with Obesity through Gut Microbiota Alterations with a Multiphase Modified Ketogenic Diet.

The occurrence of obesity and related metabolic disorders is rising, necessitating effective long-term weight management strategies. With growing interest in the potential role of gut microbes due to their association with responses to different weight loss diets, understanding the mechanisms underlying the interactions between diet, gut microbiota, and weight loss remains a challenge. This study aimed to investigate the potential impact of a multiphase dietary protocol, incorporating an improved ketogenic diet (MDP-i-KD), on weight loss and the gut microbiota. Using metagenomic sequencing, we comprehensively analyzed the taxonomic and functional composition of the gut microbiota in 13 participants before and after a 12-week MDP-i-KD intervention. The results revealed a significant reduction in BMI (9.2% weight loss) among obese participants following the MDP-i-KD intervention. Machine learning analysis identified seven key microbial species highly correlated with MDP-i-KD, with Parabacteroides distasonis exhibiting the highest response. Additionally, the co-occurrence network of the gut microbiota in post-weight-loss participants demonstrated a healthier state. Notably, metabolic pathways related to nucleotide biosynthesis, aromatic amino acid synthesis, and starch degradation were enriched in pre-intervention participants and positively correlated with BMI. Furthermore, species associated with obesity, such as Blautia obeum and Ruminococcus torques, played pivotal roles in regulating these metabolic activities. In conclusion, the MDP-i-KD intervention may assist in weight management by modulating the composition and metabolic functions of the gut microbiota. Parabacteroides distasonis, Blautia obeum, and Ruminococcus torques could be key targets for gut microbiota-based obesity interventions.

Clostridium butyricum Strain CCFM1299 Reduces Obesity via Increasing Energy Expenditure and Modulating Host Bile Acid Metabolism.

Clostridium butyricum is a butyrate-producing microorganism which has beneficial effects on various diseases, including obesity. In our previous study, the anti-obesity Clostridium butyricum strain CCFM1299 (C20_1_1) was selected, but its anti-obesity mechanism was not clarified. Herein, CCFM1299 was orally administrated to high-fat-diet-treated C57BL/6J mice for 12 weeks to uncover the way the strain alleviates obesity. The results indicated that CCFM1299 alleviated obesity through increasing the energy expenditure and increasing the expression of genes related to thermogenesis in brown adipose tissue (BAT). Moreover, strain CCFM1299 could also affect the expression of immune-related genes in epididymal white adipose tissue (eWAT). This immunomodulatory effect might be achieved through its influence on the complement system, as the expression of the complement factor D (CFD) gene decreased significantly. From the view of metabolites, CCFM1299 administration increased the levels of ursodeoxycholic acid (UDCA) in feces and taurohyodeoxycholic acid (THDCA) in serum. Together, the anti-obesity potential of CCFM1299 might be attributed to the increase in energy consumption, the regulation of immune-related gene expression in eWAT, and the alteration of bile acid metabolism in the host. These provided new insights into the potential application of anti-obesity microbial preparations and postbiotics.

Uncovering Predictive Factors and Interventions for Restoring Microecological Diversity after Antibiotic Disturbance.

Antibiotic treatment can lead to a loss of diversity of gut microbiota and may adversely affect gut microbiota composition and host health. Previous studies have indicated that the recovery of gut microbes from antibiotic-induced disruption may be guided by specific microbial species. We expect to predict recovery or non-recovery using these crucial species or other indices after antibiotic treatment only when the gut microbiota changes. This study focused on this prediction problem using a novel ensemble learning framework to identify a set of common and reasonably predictive recovery-associated bacterial species (p-RABs), enabling us to predict the host microbiome recovery status under broad-spectrum antibiotic treatment. Our findings also propose other predictive indicators, suggesting that higher taxonomic and functional diversity may correlate with an increased likelihood of successful recovery. Furthermore, to explore the validity of p-RABs, we performed a metabolic support analysis and identified Akkermansia muciniphila and Bacteroides uniformis as potential key supporting species for reconstruction interventions. Experimental results from a C57BL/6J male mouse model demonstrated the effectiveness of p-RABs in facilitating intestinal microbial reconstitution. Thus, we proved the reliability of the new p-RABs and validated a practical intervention scheme for gut microbiota reconstruction under antibiotic disturbance.

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.