Maternal obesity poses a significant threat to the metabolic profiles of offspring. Microorganisms acquired from the mother early in life critically affect the host's metabolic functions. Natural non-nutritive sweeteners, particularly stevioside (STV), play a crucial role in reducing obesity and affecting gut microbiota composition. Based on this, we hypothesized that maternal STV supplementation could improve the health of mothers and offspring by altering their gut microbiota. Our study found that maternal STV supplementation reduced obesity during pregnancy, decreased abnormal lipid accumulation in offspring mice caused by maternal obesity, and modified the gut microbiota of both dams and offspring, notably increasing the abundance of Lactobacillus apodemi (L. apodemi). Co-housing and fecal microbiota transplant experiments confirmed that gut microbiota mediated the effects of STV on metabolic disorders. Furthermore, treatment with L. apodemi alone replicated the beneficial effects of STV, which were associated with increased thermogenesis. In summary, maternal STV supplementation could alleviate lipid metabolic disorders in offspring by enhancing L. apodemi levels and promoting thermogenic activity, potentially involving changes in bile acid metabolism pathways.

Bifidobacterium breve is a well-recognized probiotic species. B. breve JKL2022, a strain isolated from the feces of healthy infants that exhibits superior conjugated linoleic acid (CLA)-converting activity, was functionally characterized for probiotic safety and applicability through genomic and in vitro analyses. The JKL2022 genome comprises a 2,313,948 bp sequence assembled into a single contig, encoding a total of 1,998 genes. In silico predictive analyses confirmed the absence of virulence factors and acquired resistance genes while verifying its intrinsic antimicrobial resistance profile. Several CAZymes were identified, consistent with the strain's fermentation profile. Additionally, the gene encoding the key enzyme for CLA conversion was identified as a 993-bp lai gene, underscoring the species-level differences in microbial CLA metabolism. The functionality, stress tolerance, and safety of JKL2022 were further confirmed through experimental assessments. JKL2022 exhibited tolerance to acid and bile salts, auto-aggregation, and cell surface hydrophobicity, indicating its potential to survive gastrointestinal transit. Furthermore, JKL2022 exhibited α-glucosidase inhibitory activity and tested negative for starch hydrolysis, hemolysis, and gelatinase activity. The inherent probiotic properties of Bifidobacterium, combined with the strain-specific CLA conversion using growing cells and postbiotic preparations, contribute to the potential health benefits of B. breve JKL2022, as verified in this study.

Quorum sensing (QS) is a common method of communication among bacteria. While previous studies have discovered the mechanisms of QS in a variety of pathogenic bacteria, relatively little research has focused on probiotics, such as Bifidobacteria. Recent studies have detected QS signalling molecules in Bifidobacteria, but it remains unclear whether the probiotic properties of Bifidobacteria are mediated by QS. This review aims to provide an overview of the QS system in Bifidobacteria and its role in promoting the secretion of metabolites such as extracellular vesicles and biofilms. The review further examines the inhibition of virulence gene expression by Bifidobacteria QS through the luxS/AI-2 system, as well as its role in promoting host-microbial interactions. Understanding the QS mechanisms of Bifidobacteria can reveal beneficial interactions with hosts, which may facilitate the control of bacterial infections, including therapeutic strategies for intestinal diseases. This knowledge can also help improve gut health, thereby addressing the opportunities and challenges of enhancing the body's nutritional status.

Micronutrient deficiencies (MNDs) impact more than three billion individuals worldwide, particularly those in impoverished and marginalized communities, leading to adverse long-term health consequences. Biofortification, which focusses on enhancing the nutrient density of food crops, presents a promising strategy to address this challenge. Recent studies involving both model organisms and human subjects have demonstrated that, beyond remedying common dietary insufficiencies, micronutrients can modulate the composition and functionality of the gut microbiome. The microbiota, in turn, utilize these micronutrients, facilitating digestion, synthesizing essential nutrients, and modulating immune responses, thereby establishing a bidirectional relationship known as the micronutrient-microbiome axis. Numerous studies have also documented significant variations in these interactions, highlighting the complex dynamics of the micronutrient-microbiome relationship. The composition and interactions of the microbiota have been investigated using various methodologies, including 16S rRNA gene sequencing, RT-PCR, metagenomics, and metabolomics. This review explores recent advancements in understanding the reciprocal relationship between micronutrient levels and the gut microbiome, emphasizing key findings that provide critical insights for the development of targeted dietary strategies aimed at alleviating MNDs and improving overall health.

The gut microbiome of women can change after menopause, and during this phase women can also be more susceptible to vaginal dysbiosis. Recent studies have explored the probiotic potential of Lactobacillus crispatus BC4 and Lactobacillus gasseri BC9 against various pathogens and their use as co-starters in foods. However, their effects on the gut microbiota of post-menopausal women, who are more prone to dysbiosis, have not been examined. This study investigated the effects of predigested soy beverages (INFOGEST) containing BC4 and BC9 (encapsulated or not) on the composition and metabolic activity of the gut microbiota in post-menopausal women, using a fecal batch culture model. Parameters such as pH, gas, SCFAs, and microbiota composition (targeted qPCR and 16S rRNA gene sequencing) were assessed. The study, while highlighting a strong variability among donors, showed differences in gut microbiota response to the tested products. For instance, donor 2 showed a significant increase in bifidobacteria with BC4 + BC9 and E-BC9, while BC4 increased Ruminococcaceae in donors 1 and 3, and E-BC4 and E-BC9 enhanced Akkermansia in donor 1. BC4, E-BC4, E-BC9, and E-BC4 + BC9 significantly impacted metabolic activity, as measured by SCFAs, compared to other samples. However, no significant differences in gas production were observed.

The health status of the growing infant is closely related to the development of the gut microbiota during infancy, which is also a major stimulator of the immune system. Goat milk oligosaccharides (gMOs) are a class of bioactive compounds in goat milk, which have attracted extensive research interest in recent years. Recent studies have highlighted that gMOs as prebiotics can regulate the gut microbiota, exhibit multiple health effects, and act as immunomodulators. This article outlines the structure, classification, and functions of gMOs. In addition, we also deeply explored the mechanism of gMO interaction with infant gut microbiota and regulation of infant immunity. Finally, the possibility of gMOs as an effective substitute for natural prebiotics in breast milk is revisited. We concluded that gMOs improve infant immune function by regulating intestinal beneficial bacteria (Bifidobacteria, Lactobacilli, etc.) and their metabolism. Therefore, gMOs are significant to infant immune health and are expected to become a substitute for human milk oligosaccharides (HMOs).

2'-Fucosyllactose (2'-FL), one of the most representative oligosaccharides in human milk, is intimately linked to the enrichment of specific Bifidobacterium species. However, the efficacy of 2'-FL in modulating the probiotic responses of bifidobacterium has been rarely researched. Thereinto, three key issues have yet to be reported: the effects of 2'-FL hydrolysis on bifidobacterial growth, the protective effects of 2'-FL on bifidobacterium under gastrointestinal stress and the inhibitory activity of 2'-FL metabolites against Cronobacter spp. This work intended to address these concerns. 2'-FL dramatically accelerated the growth and proliferation of Bifidobacterium bifidum YH17 and Bifidobacterium bifidum BBI01. The glucose in lactose core on 2'-FL was preferable for B. bifidum to achieve substantial increases in biomass while the galactose was not readily available. Additionally, 2'-FL showed unique advantages in ameliorating the resistance of B. bifidum to gastrointestinal challenges. 2'-FL considerably improved the adhesive property of B. bifidum, thus facilitating the competitive elimination of Cronobacter sakazakii ATCC 29544 and Cronobacter muytjensii ATCC 51329 by B. bifidum. The growth inhibition of 2'-FL on the Cronobacter strains was mediated by promoting the secretion of antibacterial substances from B. bifidum. The inhibitory activity hinged on the B. bifidum strains. 2'-FL specifically induced B. bifidum BBI01 to produce some antibacterial substances that were proteinaceous, thermostable and relatively stable even at pH 8.0. These antibacterial substances played a key role in the inhibitory activity and had a synergistic effect with acidification. These observations provide a useful guideline for developing synbiotic supplements to intervene the infant gut microbiota.

Cholera, a disease caused by Vibrio cholerae, remains a pervasive public health threat, particularly in regions with inadequate water sanitation and hygiene infrastructure, such as Bangladesh. This review explores the complex interplay between water pollution and cholera transmission in Bangladesh, highlighting how contaminated water bodies serve as reservoirs for V. cholerae. A key focus is the potential role of probiotics as a novel intervention approach for cholera prevention and management. Probiotics are promising as an adjunctive approach to existing therapies as they can enhance gut barrier function, induce competitive exclusion of pathogens, and modulate host immune responses. Recent probiotic advancements include engineering strains that disrupt V. cholerae biofilms and inhibit their virulence. Integrating probiotics with traditional cholera control measures could significantly enhance their effectiveness and provide a multifaceted approach to combating this persistent disease. This review aims to shed light on the potential of probiotics in revolutionizing cholera management and to offer insights into their application as both preventive and therapeutic tools in the fight against this enduring public health challenge.

Probiotics, prebiotics, and postbiotics can significantly influence B-cell-related diseases through their immunomodulatory effects. They enhance the immune system's function, particularly affecting B cells, which originate in the bone marrow and are crucial for antibody production and immune memory. These substances have therapeutic potential in managing allergies, autoimmune diseases, and inflammatory conditions by regulating the gut microbiota, strengthening epithelial barriers, and directly interacting with various components of the innate and adaptive immune systems. The review highlights the critical need for further research into the precise mechanisms through which probiotics, prebiotics, and postbiotics modulate B cells. Gaining this understanding could facilitate the development of more effective treatments for B-cell-related diseases by harnessing the immunomodulatory properties of these dietary components.

Background: the intestinal microbiota, a complex community vital to human health, is shaped by microbial competition and host-driven selective pressures. Among these microbes, Bifidobacterium plays a crucial role in early gut colonization during neonatal stages, where Bifidobacterium longum subspecies infantis (B. infantis) predominates and is particularly prevalent in healthy breastfed infants. Objectives: as we embark on a new era in nutrition of the pediatric population, this study seeks to examine the existing understanding regarding B. infantis, encompassing both preclinical insights and clinical evidence. Methods: through a narrative disceptation of the current literature, we focus on its genetic capacity to break down various substances that support its survival and dominance in the intestine. Results: using "omics" technologies, researchers have identified beneficial mechanisms of B. infantis, including the production of short-chain fatty acids, serine protease inhibitors, and polysaccharides. While B. infantis declines with age and in various diseases, it remains a widely used probiotic with documented benefits for infant and child health in numerous studies. Conclusions: the current scientific evidence underscores the importance for ongoing research and clinical trials for a deeper understanding of B. infantis's role in promoting long-term health.

Bifidobacteria are well known as common and abundant colonizers of the human gut and are able to exert multiple beneficial effects on their host, although the cooperative and competitive relationships that may occur among bifidobacterial strains are still poorly investigated. Therefore, to dissect possible molecular interactions among bifidobacterial species that typically colonize the human gut, three previously identified bifidobacterial prototypes, i.e., B. bifidum PRL2010, B. breve PRL2012, and B. longum PRL2022 were cultivated individually as well as in bi- and tri-association in a human gut-simulating medium. Transcriptomic analyses of these co-associations revealed up-regulation of genes predicted to be involved in the production of extracellular structures including pili (i.e., flp pilus assembly TadE protein gene), exopolysaccharides (i.e., GtrA family protein gene) and teichoic acids (i.e., ABC transporter permease), along with carbohydrate, amino acid and vitamin metabolism-related genes (i.e., exo-alpha-sialidase; beta-galactosidase and pyridoxamine kinase), suggesting that co-cultivation of bifidobacteria induces a response, in individual bifidobacterial strains, aimed at enhancing their proliferation and survival, as well as their ability to cooperate with their host to promote their persistence. Furthermore, exposure of the selected prototypes to human cell line monolayers unveiled the ability of the bifidobacterial tri-association to communicate with their host by increasing the expression of genes involved in adherence to/interaction with intestinal human cells. Lastly, bifidobacterial tri-association promoted the transcriptional upregulation of genes responsible for maintaining the integrity and homeostasis of the intestinal epithelial barrier.

Exploring probiotics for their crosstalk with the host microbiome through the fermentation of non-digestible dietary fibers (prebiotics) for their potential metabolic end-products, particularly short-chain fatty acids (SCFAs), is important for understanding the endogenous host-gut microbe interaction. This study was aimed at a systematic comparison of commercially available probiotics to understand their synergistic role with specific prebiotics in SCFAs production both in vitro and in the ex vivo gut microcosm model. Probiotic strains isolated from pharmacy products including Lactobacillus sporogenes (strain not labeled), Lactobacillus rhamnosus GG (ATCC53103), Streptococcus faecalis (T-110 JPC), Bacillus mesentericus (TO-AJPC), Bacillus clausii (SIN) and Saccharomyces boulardii (CNCM I-745) were assessed for their probiotic traits including survival, antibiotic susceptibility, and antibacterial activity against pathogenic strains. Our results showed that the microorganisms under study had strain-specific abilities to persist in human gastrointestinal conditions and varied anti-infective efficacy and antibiotic susceptibility. The probiotic strains displayed variation in the utilization of six different prebiotic substrates for their growth under aerobic and anaerobic conditions. Their prebiotic scores (PS) revealed which were the most suitable prebiotic carbohydrates for the growth of each strain and suggested xylooligosaccharide (XOS) was the poorest utilized among all. HPLC analysis revealed a versatile pattern of SCFAs produced as end-products of prebiotic fermentation by the strains which was influenced by growth conditions. Selected synbiotic (prebiotic and probiotic) combinations showing high PS and high total SCFAs production were tested in an ex vivo human gut microcosm model. Interestingly, significantly higher butyrate and propionate production was found only when synbiotics were applied as against when individual probiotic or prebiotics were applied alone. qRT-PCR analysis with specific primers showed that there was a significant increase in the abundance of lactobacilli and bifidobacteria with synbiotic blends compared to pre-, or probiotics alone. In conclusion, this work presents findings to suggest prebiotic combinations with different well-established probiotic strains that may be useful for developing effective synbiotic blends.

In recent years, the gut microbiome has gained significant attention in the spheres of research and public health. As a result, studies have increasingly explored the potential of probiotic dietary supplements as treatment interventions for conditions such as anxiety and depression. The present study examined the effect of mixed probiotics (Lacticaseibacillus rhamnosus and Enterococcus faecium) on inflammation, microbiome composition, and depressive-like behaviors in a macaque monkey model. The mixed probiotics effectively reduced the severity of depressive-like behaviors in macaque monkeys. Further, treatment with mixed probiotics gradually increased the abundance of beneficial bacteria in the gut, improving the balance of the gut microbiota. Additionally, macaques treated with the mixed probiotics showed decreased serum levels of inflammatory factors (P < 0.05), an increased rate of L-tryptophan metabolism (P < 0.05), and the restoration of 5-HT and 5-HTP levels (P < 0.05). Correlation analysis confirmed that Lacticaseibacillus and other beneficial bacteria exhibited a negative correlation with inflammation in the body (P < 0.05), and a positive correlation with tryptophan metabolism (P < 0.05). In conclusion, the mixed probiotics effectively restored intestinal homeostasis in macaques and enhanced tryptophan metabolism, ultimately alleviating inflammation and depressive-like behaviors.

A healthy gut microbiome is crucial for the immune system and overall development of infants. Bifidobacterium has been known to be a predominant species in the infant gut; however, an emerging concern is the apparent loss of this genus, in particular, Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiome of infants in industrialized nations, underscoring the importance of restoring this beneficial bacterium. With the growing understanding of the gut microbiome, probiotics, especially infant-type human-residential bifidobacteria (HRB) strains like B. infantis, are gaining prominence for their unique ability to utilize HMOs and positively influence infant health. This article delves into the physiology of a probiotic strain, B. infantis M-63, its symbiotic relationship with HMOs, and its potential in improving gastrointestinal and allergic conditions in infants and children. Moreover, this article critically assesses the role of HMOs and the emerging trend of supplementing infant formulas with the prebiotic HMOs, which serve as fuel for beneficial gut bacteria, thereby emulating the protective effects of breastfeeding. The review highlights the potential of combining B. infantis M-63 with HMOs as a feasible strategy to improve health outcomes in infants and children, acknowledging the complexities and requirements for further research in this area.

An imbalanced gut microflora may contribute to immune disorders in neonates due to an immature gut barrier. Bacterial toxins, particularly, can trigger the immune system, potentially resulting in uncontrolled gut and systemic inflammation. Previous research has revealed that Bifidobacterium animalis subsp. lactis (B. lactis) could protect against early-life pathogen infections by enhancing the gut barrier. However, the effects of B. lactis on a compromised immune system remain uncertain. Hence, this study concentrated on the immunomodulatory effects and mechanisms of B. lactis in neonatal rats intraperitoneally injected with lipopolysaccharide (LPS), a bacterial toxin and inflammatory mediator. First, B. lactis significantly alleviated the adverse effects induced by LPS on the growth, development, and body temperature of neonatal rats. Second, B. lactis significantly reduced the immune responses and damage induced by LPS, affecting both systemic and local immune responses in the peripheral blood, gut, and brain. Notably, B. lactis exhibited extra potent neuroprotective and neurorepair effects. Our research found that pre-treatment with B. lactis shaped the diverse gut microecology by altering both microbial populations and metabolic biomolecules, closely linked to immunomodulation. Overall, this study elucidated the multifaceted roles of B. lactis in neonatal hosts against pathogenic infection and immune disorder, revealing the existence of the microbiota-gut-brain axis.

Recent studies suggest that the dietary intake of human milk oligosaccharides (HMOs) provides health benefits from infancy up to adulthood. Thus far, beneficial changes in the adult gut microbiome have been observed at oral doses of 5-20 g/day of HMOs. Efficacy of lower doses has rarely been tested. We assessed four HMO molecular species-2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), and 6'Sialyllactose (6'SL)-at predicted doses from 0.3 to 5 g/day for 6-year-old children and adults (n = 6 each), using ex vivo SIFR® technology (Cryptobiotix, Ghent, Belgium). This technology employing bioreactor fermentation on fecal samples enables us to investigate microbial fermentation products that are intractable in vivo given their rapid absorption/consumption in the human gut. We found that HMOs significantly increased short-chain fatty acids (SCFAs), acetate, propionate (in children/adults), and butyrate (in adults) from predicted doses of 0.3-0.5 g/day onwards, with stronger effects as dosing increased. The fermentation of 6'SL had the greatest effect on propionate, LNnT most strongly increased butyrate, and 2'FL and 3'SL most strongly increased acetate. An untargeted metabolomic analysis revealed that HMOs enhanced immune-related metabolites beyond SCFAs, such as aromatic lactic acids (indole-3-lactic acid/3-phenyllactic acid) and 2-hydroxyisocaproic acid, as well as gut-brain-axis-related metabolites (γ-aminobutyric acid/3-hydroxybutyric acid/acetylcholine) and vitamins. The effects of low doses of HMOs potentially originate from the highly specific stimulation of keystone species belonging to, for example, the Bifidobacteriaceae family, which had already significantly increased at doses of only 0.5 g/day LNnT (adults) and 1 g/day 2'FL (children/adults).

Kanpyo (KP) is an edible dried product produced by peeling the fruit of the gourd Lagenaria siceraria var. hispida; it is used in the traditional Japanese cuisine. The health functionality of KP due to its rich dietary fibre is expected to include a possible combined effect of KP-responsive indigenous gut bacteria (KP-RIB). However, its effect on the gut microbiota is unclear. To determine the effects of the KP on the gut microbiota and their host, Institute of Cancer Research mice were fed a high-sucrose diet containing no fibre (NF) or 5% (w/w) KP for 14 days, and their caecal microbiota was analysed by 16S rRNA (V4) amplicon sequencing. Higher faecal frequency and weight and lower spleen weight and spleen tumour necrosis factor-α levels were observed in KP-fed mice than in NF-fed mice (p < 0.05). KP increased and decreased the abundance of short-chain fatty acid producer Lachnospiraceae and obesity-inflammation related Allobaculum species, respectively. In the case of human faecal cultures, stool samples from five healthy volunteers were inoculated and incubated at 37 °C for 24 h anaerobically; 3.2% (w/v) KP suppressed putrefactive compounds (indole, phenol, and ammonia). KP increased butyrate-producer Faecalibacterium, acetate/lactate-producer Bifidobacterium, and Lachnospira. Furthermore, KP cultures showed high antioxidant and RAW264.7 macrophage cell activation capacities. These results suggest that KP-RIB and KP intake may synergistically affect host health. However, further studies are required to clarify the synergistic effects of KP and KP-RIB.

Bifidobacterium longum subsp. infantis is a representative and dominant species in the infant gut and is considered a beneficial microbe. This organism displays multiple adaptations to thrive in the infant gut, regarded as a model for human milk oligosaccharides (HMOs) utilization. These carbohydrates are abundant in breast milk and include different molecules based on lactose. They contain fucose, sialic acid, and N-acetylglucosamine. Bifidobacterium metabolism is complex, and a systems view of relevant metabolic pathways and exchange metabolites during HMO consumption is missing. To address this limitation, a refined genome-scale network reconstruction of this bacterium is presented using a previous reconstruction of B. infantis ATCC 15967 as a template. The latter was expanded based on an extensive revision of genome annotations, current literature, and transcriptomic data integration. The metabolic reconstruction (iLR578) accounted for 578 genes, 1,047 reactions, and 924 metabolites. Starting from this reconstruction, we built context-specific genome-scale metabolic models using RNA-seq data from cultures growing in lactose and three HMOs. The models revealed notable differences in HMO metabolism depending on the functional characteristics of the substrates. Particularly, fucosyl-lactose showed a divergent metabolism due to a fucose moiety. High yields of lactate and acetate were predicted under growth rate maximization in all conditions, whereas formate, ethanol, and 1,2-propanediol were substantially lower. Similar results were also obtained under near-optimal growth on each substrate when varying the empirically observed acetate-to-lactate production ratio. Model predictions displayed reasonable agreement between central carbon metabolism fluxes and expression data across all conditions. Flux coupling analysis revealed additional connections between succinate exchange and arginine and sulfate metabolism and a strong coupling between central carbon reactions and adenine metabolism. More importantly, specific networks of coupled reactions under each carbon source were derived and analyzed. Overall, the presented network reconstruction constitutes a valuable platform for probing the metabolism of this prominent infant gut bifidobacteria.IMPORTANCEThis work presents a detailed reconstruction of the metabolism of Bifidobacterium longum subsp. infantis, a prominent member of the infant gut microbiome, providing a systems view of its metabolism of human milk oligosaccharides.

Bifidobacteria are commensal microorganisms that typically inhabit the mammalian gut, including that of humans. As they may be vertically transmitted, they commonly colonize the human intestine from the very first day following birth and may persist until adulthood and old age, although generally at a reduced relative abundance and prevalence compared to infancy. The ability of bifidobacteria to persist in the human intestinal environment has been attributed to genes involved in adhesion to epithelial cells and the encoding of complex carbohydrate-degrading enzymes. Recently, a putative mucin-degrading glycosyl hydrolase belonging to the GH136 family and encoded by the perB gene has been implicated in gut persistence of certain bifidobacterial strains. In the current study, to better characterize the function of this gene, a comparative genomic analysis was performed, revealing the presence of perB homologues in just eight bifidobacterial species known to colonize the human gut, including Bifidobacterium bifidum and Bifidobacterium longum subsp. longum strains, or in non-human primates. Mucin-mediated growth and adhesion to human intestinal cells, in addition to a rodent model colonization assay, were performed using B. bifidum PRL2010 as a perB prototype and its isogenic perB-insertion mutant. These results demonstrate that perB inactivation reduces the ability of B. bifidum PRL2010 to grow on and adhere to mucin, as well as to persist in the rodent gut niche. These results corroborate the notion that the perB gene is one of the genetic determinants involved in the persistence of B. bifidum PRL2010 in the human gut.

A well-balanced diet is integral for overall health, aiding in managing key risk factors for kidney damage like hypertension while supplying necessary precursors for metabolite production. Dietary choices directly influence the composition and metabolic patterns of the gut microbiota, showing promise as therapeutic tools for addressing various health conditions, including chronic kidney diseases (CKD). CKD pathogenesis involves a decline in the glomerular filtration rate and the retention of nitrogen waste, fostering gut dysbiosis and the excessive production of bacterial metabolites. These metabolites act as uremic toxins, contributing to inflammation, oxidative stress, and tissue remodeling in the kidneys. Dietary interventions hold significance in reducing oxidative stress and inflammation, potentially slowing CKD progression. Functional ingredients, nutrients, and nephroprotective phytoconstituents could modulate inflammatory pathways or impact the gut mucosa. The "gut-kidney axis" underscores the impact of gut microbes and their metabolites on health and disease, with dysbiosis serving as a triggering event in several diseases, including CKD. This review provides a comprehensive overview, focusing on the gut-liver axis, and explores well-established bioactive substances as well as specific, less-known nutraceuticals showing promise in supporting kidney health and positively influencing CKD progression.

The early-life gut microbiome development has long-term health impacts and can be influenced by factors such as infant diet. Human milk oligosaccharides (HMOs), an essential component of breast milk that can only be metabolized by some beneficial gut microorganisms, ensure proper gut microbiome establishment and infant development. However, how HMOs are metabolized by gut microbiomes is not fully elucidated. Isolate studies have revealed the genetic basis for HMO metabolism, but they exclude the possibility of HMO assimilation via synergistic interactions involving multiple organisms. Here, we investigate microbiome responses to 2'-fucosyllactose (2'FL), a prevalent HMO and a common infant formula additive, by establishing individualized microbiomes using fecal samples from three infants as the inocula. Bifidobacterium breve, a prominent member of infant microbiomes, typically cannot metabolize 2'FL. Using metagenomic data, we predict that extracellular fucosidases encoded by co-existing members such as Ruminococcus gnavus initiate 2'FL breakdown, thus critical for B. breve's growth. Using both targeted co-cultures and by supplementation of R. gnavus into one microbiome, we show that R. gnavus can promote extensive growth of B. breve through the release of lactose from 2'FL. Overall, microbiome cultivation combined with genome-resolved metagenomics demonstrates that HMO utilization can vary with an individual's microbiome.

The vital role of probiotics in the food field has been widely recognized, and at the same time, probiotics are gradually exhibiting surprising effects in the field of nutraceuticals, especially in regulating gut inflammation and the nutritional environment. As a dietary supplement in clinical nutrition, the coadministration of probiotics with antibiotics model has been applied to prevent intestinal infections caused by Clostridioides difficile. However, the mechanism behind this "bacteria-drug combination" model remains unclear. In particular, the selection of specific probiotic strains, the order of probiotics or antibiotics, and the time interval of coadministration are key issues that need to be further explored and clarified. Here, we focus on the issues mentioned above and give reasonable opinions, mainly including: (1) probiotics are safer and more effective when they intervene after antibiotics have been used; (2) the choice of the time interval between coadministration should be based on the metabolism of antibiotics in the host, differences in probiotic strains, the baseline ecological environment of the host's intestine, and the host immune level; in addition, the selection of the coadministration regime should also take into account factors such as the antibiotic sensitivity of probiotics and dosage of probiotics; and (3) by encapsulating probiotics, combining probiotics with prebiotics, and developing next-generation probiotics (NGPs) and postbiotic formulations, we can provide a more reasonable reference for this type of "bacteria-drug combination" model, and also provide targeted guidance for the application of probiotic dietary supplements in the antibiotic management of C. difficile infection.

Bifidobacterium species are integral members of the human gut microbiota and these microbes have significant interactions with the intestinal mucus layer. This review delves into Bifidobacterium-mucus dynamics, shedding light on the multifaceted nature of this relationship. We cover conserved features of Bifidobacterium-mucus interactions, such as mucus adhesion and positive regulation of goblet cell and mucus production, as well as species and strain-specific attributes of mucus degradation. For each interface, we explore the molecular mechanisms underlying these interactions and their potential implications for human health. Notably, we emphasize the ability of Bifidobacterium species to positively influence the mucus layer, shedding light on its potential as a mucin-builder and a therapeutic agent for diseases associated with disrupted mucus barriers. By elucidating the complex interplay between Bifidobacterium and intestinal mucus, we aim to contribute to a deeper understanding of the gut microbiota-host interface and pave the way for novel therapeutic strategies.

Recently, the research on pig intestinal microbiota has become a hot topic in the field of animal husbandry. There are few articles describing the dynamic changes of porcine fecal microbiota and metabolites at different time points from birth to market.

In the present study, 381 fecal samples were collected from 633 commercial pigs at 7 time points, including the 1st day, the 10th day, the 25th day, the 45th day, the 70th day, the 120th day, and the 180th day after the birth of swine, were used for microbiome analysis by Illumina MiSeq sequencing methods while 131 fecal samples from 3 time points, the 10th day, the 25th day, and 70th day after birth, were used for metabolome analysis by LC-MS methods.

For the microbiome analysis, the fecal microbial richness increased over time from day 1 to 180 and the β-diversity of fecal microbiota was separated significantly at different time points. Firmicutes were the main phyla from day 10 to 180, followed by Bacteroides. The abundance of Lactobacillus increased significantly on day 120 compared with the previous 4 time points. From day 120 to day 180, the main porcine fecal microbes were Lactobacillus, Clostridium_sensu_stricto_1, Terrisporobacter and Streptococcus. Clostridium_sensu_stricto_1 and Terrisporobacter increased over time, while Lactobacillus, Escherichia-Shigella, Lachnoclostridium decreased with the time according to the heatmap, which showed the increase or decrease in microbial abundance over time. For the metabolome analysis, the PLS-DA plot could clearly distinguish porcine fecal metabolites on day 10, 25, and 70. The most different metabolic pathways of the 3 time points were Tryptophan metabolism, Sphingolipid signaling pathway, Protein digestion and absorption. Some metabolites increased significantly over time, such as Sucrose, L-Arginine, Indole, 2,3-Pyridinedicarboxylic acid and so on, while D-Maltose, L-2-Aminoadipic acid, 2,6-diaminohexanoic acid, L-Proline were opposite. The correlation between fecal metabolites and microbiota revealed that the microbes with an increasing trend were positively correlated with the metabolites affecting the tryptophan metabolic pathway from the overall trend, while the microbes with a decreasing trend were opposite. In addition, the microbes with an increasing trend were negatively correlated with the metabolites affecting the lysine pathway.

In conclusion, this study elucidated the dynamic changes of porcine fecal microbiota and metabolites at different stages from birth to market, which may provide a reference for a comprehensive understanding of the intestinal health status of pigs at different growth stages.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by deficits in social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome-gut-brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function and microbiota metabolites in ASD. However, a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity and the microbiome-gut-brain axis in the development of autistic symptoms severity and a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via the microbiome-gut-brain axis in a feedback circuit.

Background: At birth, the human intestine is colonized by a complex community of microorganisms known as gut microbiota. These complex microbial communities that inhabit the gut microbiota are thought to play a key role in maintaining host physiological homeostasis. For this reason, correct colonization of the gastrointestinal tract in the early stages of life could be fundamental for human health. Furthermore, alterations of the infant microbiota are correlated with the development of human inflammatory diseases and disorders. In this context, the possible relationships between intestinal microbiota and body composition during infancy are of great interest. Methods: In this study, we have performed a pilot study based on 16S rRNA gene profiling and metagenomic approaches on repeatedly measured data on time involving a cohort of 41 Italian newborns, which is aimed to investigate the possible correlation between body fat mass percentage (FM%) and the infant gut microbiota composition. Results and conclusion: The taxonomical analysis of the stool microbiota of each infant included in the cohort allowed the identification of a specific correlation between intestinal bacteria, such as Bifidobacterium and Veillonella, and the increase in FM%. Moreover, the analysis of the infant microbiome's metabolic capabilities suggested that the intestinal microbiome functionally impacts the human host and its possible influence on host physiology.

A significant proportion of the infant gut microbiome is considered to be acquired from the mother during and after birth. Thus begins a lifelong and dynamic relationship with microbes that has an enduring impact on host health. Based on a cohort of 135 mother-infant (F = 72, M = 63) dyads (MicrobeMom: ISRCTN53023014), we investigated the phenomenon of microbial strain transfer, with a particular emphasis on the use of a combined metagenomic-culture-based approach to determine the frequency of strain transfer involving members of the genus Bifidobacterium, including species/strains present at low relative abundance. From the isolation and genome sequencing of over 449 bifidobacterial strains, we validate and augment metagenomics-based evidence to reveal strain transfer in almost 50% of dyads. Factors important in strain transfer include vaginal birth, spontaneous rupture of amniotic membranes, and avoidance of intrapartum antibiotics. Importantly, we reveal that several transfer events are uniquely detected employing either cultivation or metagenomic sequencing, highlighting the requirement for a dual approach to obtain an in-depth insight into this transfer process.

Bifidobacterium species are known for their ability to inhabit various habitats and are often regarded as the first colonisers of the human gut. In the present work, we have used comparative genomics to identify conserved genomic signatures specific to Bifidobacterium species associated with the human gut. Our approach discovered five genomic signatures with varying lengths and confidence. Among the predicted five signatures, a 1790 bp multi-drug resistance (MDR) signature was found to be remarkably specific to only those species that can colonise the human gut. The signature codes for a membrane transport protein belonging to the major facilitator superfamily (MFS) generally involved in MDR. Phylogenetic analyses of the MDR signature suggest a lineage-specific evolution of the MDR signature in bifidobacteria colonising the human gut. Functional annotation led to the discovery of two conserved domains in the protein; a catalytic MFS domain involved in the efflux of drugs and toxins, and a regulatory cystathionine-β-synthase (CBS) domain that can interact with adenosyl-carriers. Molecular docking simulation performed with the modelled tertiary structure of the MDR signature revealed the putative functional role of the covalently linked domains. The MFS domain displayed a high affinity towards various protein synthesis inhibitor antibiotics and human bile acids, whereas the C-terminally linked CBS domain exhibited favourable binding with molecular structures of ATP and AMP. Therefore, we believe that the predicted signature represents a niche-specific survival trait involved in bile and antibiotic resistance, imparting an adaptive advantage to the Bifidobacterium species colonising the human gut.

The online version contains supplementary material available at 10.1007/s13205-023-03492-4.

The infants' gut microbiome is dynamic in nature. Literature has shown high inter-individual variability of gut microbial composition in the early years of infancy compared to adulthood. Although next-generation sequencing technologies are rapidly evolving, several statistical analysis aspects need to be addressed to capture the variability and dynamic nature of the infants' gut microbiome. In this study, we proposed a Bayesian Marginal Zero-inflated Negative Binomial (BAMZINB) model, addressing complexities associated with zero-inflation and multivariate structure of the infants' gut microbiome data. Here, we simulated 32 scenarios to compare the performance of BAMZINB with glmFit and BhGLM as the two other widely similar methods in the literature in handling zero-inflation, over-dispersion, and multivariate structure of the infants' gut microbiome. Then, we showed the performance of the BAMZINB approach on a real dataset using SKOT cohort (I and II) studies. Our simulation results showed that the BAMZINB model performed as well as those two methods in estimating the average abundance difference and had a better fit for almost all scenarios when the signal and sample size were large. Applying BAMZINB on SKOT cohorts showed remarkable changes in the average absolute abundance of specific bacteria from 9 to 18 months for infants of healthy and obese mothers. In conclusion, we recommend using the BAMZINB approach for infants' gut microbiome data taking zero-inflation and over-dispersion properties into account in multivariate analysis when comparing the average abundance difference.

Biological systems respond to environmental perturbations and a large diversity of compounds through gene interactions, and these genetic factors comprise complex networks. Experimental information from transcriptomic studies has allowed the identification of gene networks that contribute to our understanding of microbial adaptations. In this study, we analyzed the gene co-expression networks of three Bifidobacterium species in response to different types of human milk oligosaccharides (HMO) using weighted gene co-expression analysis (WGCNA). RNA-seq data obtained from Geo Datasets were obtained for Bifidobacterium longum subsp. Infantis, Bifidobacterium bifidum and Bifidobacterium longum subsp. Longum. Between 10 and 20 co-expressing modules were obtained for each dataset. HMO-associated genes appeared in the modules with more genes for B. infantis and B. bifidum, in contrast with B. longum. Hub genes were identified in each module, and in general they participated in conserved essential processes. Certain modules were differentially enriched with LacI-like transcription factors, and others with certain metabolic pathways such as the biosynthesis of secondary metabolites. The three Bifidobacterium transcriptomes showed distinct regulation patterns for HMO utilization. HMO-associated genes in B. infantis co-expressed in two modules according to their participation in galactose or N-Acetylglucosamine utilization. Instead, B. bifidum showed a less structured co-expression of genes participating in HMO utilization. Finally, this category of genes in B. longum clustered in a small module, indicating a lack of co-expression with main cell processes and suggesting a recent acquisition. This study highlights distinct co-expression architectures in these bifidobacterial genomes during HMO consumption, and contributes to understanding gene regulation and co-expression in these species of the gut microbiome.

The gut microbiota evolves rapidly after birth, responding dynamically to environmental factors and playing a key role in short- and long-term health. Lifestyle and rurality have been shown to contribute to differences in the gut microbiome, including Bifidobacterium levels, between infants. We studied the composition, function and variability of the gut microbiomes of 6- to 11-month-old Kenyan infants (n = 105). Shotgun metagenomics showed Bifidobacterium longum to be the dominant species. A pangenomic analysis of B. longum in gut metagenomes revealed a high prevalence of B. longum subsp. infantis (B. infantis) in Kenyan infants (80%), and possible co-existence of this subspecies with B. longum subsp. longum. Stratification of the gut microbiome into community (GMC) types revealed differences in composition and functional features. GMC types with a higher prevalence of B. infantis and abundance of B. breve also had a lower pH and a lower abundance of genes encoding pathogenic features. An analysis of human milk oligosaccharides (HMOs) classified the human milk (HM) samples into four groups defined on the basis of secretor and Lewis polymorphisms revealed a higher prevalence of HM group III (Se+, Le-) (22%) than in most previously studied populations, with an enrichment in 2'-fucosyllactose. Our results show that the gut microbiome of partially breastfed Kenyan infants over the age of six months is enriched in bacteria from the Bifidobacterium community, including B. infantis, and that the high prevalence of a specific HM group may indicate a specific HMO-gut microbiome association. This study sheds light on gut microbiome variation in an understudied population with limited exposure to modern microbiome-altering factors.

The genomic era has resulted in the generation of a massive amount of genetic data concerning the genomic diversity of bacterial taxa. As a result, the microbiological community is increasingly looking for ways to define reference bacterial strains to perform experiments that are representative of the entire bacterial species. Despite this, there is currently no established approach allowing a reliable identification of reference strains based on a comprehensive genomic, ecological, and functional context. In the current study, we developed a comprehensive multi-omics approach that will allow the identification of the optimal reference strains using the Bifidobacterium genus as test case. Strain tracking analysis based on 1664 shotgun metagenomics datasets of healthy infant faecal samples were employed to identify bifidobacterial strains suitable for in silico and in vitro analyses. Subsequently, an ad hoc bioinformatic tool was developed to screen local strain collections for the most suitable species-representative strain alternative. The here presented approach was validated using in vitro trials followed by metagenomics and metatranscriptomics analyses. Altogether, these results demonstrated the validity of the proposed model for reference strain selection, thus allowing improved in silico and in vitro investigations both in terms of cross-laboratory reproducibility and relevance of research findings.

Thorough understanding of the initial colonization process of human intestines is important to optimize the prevention of microbiota-associated diseases, and also to further improve the current microbial therapies. In recent years, therefore, colonization of the human gut has gained renewed interest. However, due to a lack of standardization of life events that might influence this early colonization process in humans, many generally accepted insights are based on deduction and assumption. In our review, we compare knowledge on colonization in humans with research in piglets, because the intestinal tract of pigs is remarkably similar to that of humans and the early-life events are more standardized. We assess potential similarities and challenge some concepts that have been widely accepted in human microbiota research. Bacterial colonization of the human gut is characterized by successive waves in a progressive process, to a complex gut microbiota community. After re-analyzing available data from piglets, we found that the bacterial colonization process is very similar in terms of the wave sequence and functionality of each wave. Moreover, based on the piglet data, we found that, in addition to external factors such as suckling and nutrition, the bacterial community itself appears to have a major influence on the colonization success of additional bacteria in the intestine. Thus, the colonization process in piglets might rely, at least in part, on niche dependency, an ecological principle to be considered in the intestinal colonization process in humans.

The gastrointestinal microbiota members produce α-l-fucosidases that play key roles in mucosal, human milk, and dietary oligosaccharide assimilation. Here, 36 open reading frames (ORFs) coding for putative α-l-fucosidases belonging to glycosyl hydrolase family 29 (GH29) were identified through metagenome analysis of breast-fed infant fecal microbiome. Twenty-two of those ORFs showed a complete coding sequence with deduced amino acid sequences displaying the highest degree of identity with α-l-fucosidases from Bacteroides thetaiotaomicron, Bacteroides caccae, Phocaeicola vulgatus, Phocaeicola dorei, Ruminococcus gnavus, and Streptococcus parasanguinis. Based on sequence homology, 10 α-l-fucosidase genes were selected for substrate specificity characterization. The α-l-fucosidases Fuc18, Fuc19A, Fuc35B, Fuc39, and Fuc1584 showed hydrolytic activity on α1,3/4-linked fucose present in Lewis blood antigens and the human milk oligosaccharide (HMO) 3-fucosyllactose. In addition, Fuc1584 also hydrolyzed fucosyl-α-1,6-N-acetylglucosamine (6FN), a component of the core fucosylation of N-glycans. Fuc35A and Fuc193 showed activity on α1,2/3/4/6 linkages from H type-2, Lewis blood antigens, HMOs and 6FN. Fuc30 displayed activity only on α1,6-linked l-fucose, and Fuc5372 showed a preference for α1,2 linkages. Fuc2358 exhibited a broad substrate specificity releasing l-fucose from all the tested free histo-blood group antigens, HMOs, and 6FN. This latest enzyme also displayed activity in glycoconjugates carrying lacto-N-fucopentaose II (Lea) and lacto-N-fucopentaose III (Lex) and in the glycoprotein mucin. Fuc18, Fuc19A, and Fuc39 also removed l-fucose from neoglycoproteins and human α-1 acid glycoprotein. These results give insight into the great diversity of α-l-fucosidases from the infant gut microbiota, thus supporting the hypothesis that fucosylated glycans are crucial for shaping the newborn microbiota composition. IMPORTANCE α-l-Fucosyl residues are frequently present in many relevant glycans, such as human milk oligosaccharides (HMOs), histo-blood group antigens (HBGAs), and epitopes on cell surface glycoconjugate receptors. These fucosylated glycans are involved in a number of mammalian physiological processes, including adhesion of pathogens and immune responses. The modulation of l-fucose content in such processes may provide new insights and knowledge regarding molecular interactions and may help to devise new therapeutic strategies. Microbial α-l-fucosidases are exoglycosidases that remove α-l-fucosyl residues from free oligosaccharides and glycoconjugates and can be also used in transglycosylation reactions to synthesize oligosaccharides. In this work, α-l-fucosidases from the GH29 family were identified and characterized from the metagenome of fecal samples of breastfed infants. These enzymes showed different substrate specificities toward HMOs, HBGAs, naturally occurring glycoproteins, and neoglycoproteins. These novel glycosidase enzymes from the breast-fed infant gut microbiota, which resulted in a good source of α-l-fucosidases, have great biotechnological potential.

Human milk oligosaccharides (HMOs), multifunctional glycans naturally present in human milk, are known to contribute to the infant's microbiota and immune system development. However, the molecular specificity of HMOs on microbiota and associated fermentation is not yet fully understood, and is important for the development of infant formula optimum functionality.

In vitro fermentation is carried out on structurally different HMOs with infant fecal inocula dominated by Bifidobacterium longum, Bifidobacterium breve, and Bacteroides. The gas, metabolite (SCFA, lactate, and succinate) profiles, and microbiota responses differ between individual microbiota inocula patterns regardless of HMO structure. In terms of HMO pairs with same sugar composition but different glycosidic bonds, gas and metabolite profiles are similar with the B. longum- and B. breve-dominated inocula. However, large individual variations are observed with the Bacteroides-dominated inocula. The microbial communities at the end of fermentation are closely related to the initial microbiota composition.

The findings demonstrate that short-term in vitro fermentation outcomes largely depend on the initial gut microbiota composition more than the impact of HMO molecular specificity. These results advance the current understanding for the design of personalized infant nutritional solutions and therapies in future.

Lactobacilli and bifidobacteria are an important part of human gut microbiota. Among numerous benefits, their antioxidant properties are attracting more and more attention. Multiple in vivo and in vitro studies have demonstrated that lactobacilli and bifidobacteria, along with their cellular components, possess excellent antioxidant capacity, which provides a certain degree of protection to the human body against diseases associated with oxidative stress. Recently, lactobacilli and bifidobacteria have begun to be considered as a new source of natural antioxidants. This review summarizes the current state of research on various antioxidant properties of lactobacilli and bifidobacteria. Special emphasis is given to the mechanisms of antioxidant activity of these bacteria in the human gut microbiota, which involve bacterial cell components and metabolites. This review is also dedicated to the genes involved in the antioxidant properties of lactobacilli and bifidobacteria strains as indicators of their antioxidant potential in human gut microbiota. Identification of the antioxidant biomarkers of the gut microbiota is of great importance both for creating diagnostic systems for assessing oxidative stress and for choosing strategies aimed at restoring the normal functioning of the microbiota and, through it, restoring human health. In this review, the practical application of probiotic strains with proven antioxidant properties to prevent oxidative stress is also considered.