Ex vivo techniques can provide more physiologically significant insights into prebiotic activity and overcome some limitations of in vitro tests. In this study, an ex vivo model, formed of a large intestine of mice, was tested to assess the effects of the hydrocolloidal natural polymer, xylan (XY), and its hydrolysis product, xylooligosaccharides (XOS). XY and XOS were loaded separately into the cecum, proximal colon, and distal colon. Their utilization and short-chain fatty acid (SCFA) formation by the colonized microflora and levels of dominant phyla and key genera such as Bifidobacterium, Bacteroides, and Lactobacillus were followed. XY and XOS were metabolized in all sections, and SCFAs were released. The results suggest that the slower utilization of XY compared to XOS in the cecum can enable this polysaccharide to move towards distal parts of the large intestine and extend the sites of prebiotic activity. Unlike widely used in vitro models, the ex vivo model allowed testing the utilization pattern and effects of the prebiotics in the natural environment of the microflora and examining the intestinal sections separately.

Recent studies have emphasized the impact of gut microbiota on skin health, but the reverse, how skin diseases affect gut homeostasis, has received less attention. Allergic contact dermatitis (ACD), a common skin disorder affecting one in four people worldwide, can be accompanied by intestinal disturbances. To explore this, we used an experimental model of ACD to investigate the intestinal changes induced by the disease. Parameters assessed included intestinal microbiota, short-chain fatty acids (SCFAs), gene expression related to intestinal permeability, inflammatory cytokines, and mucus production. To evaluate potential therapeutic interventions, the probiotic Bifidobacterium longum strain BB536 was administered via gavage, starting 10 days before dermatitis induction and continuing until the last day of disease induction. ACD caused alterations in the composition of intestinal microbiota compared to naïve mice but did not affect SCFA production. The probiotic altered microbiota composition and increased acetate production in dermatitis-induced mice. ACD decreased the gene expression of TjP1, ATHO1, and MUC2, while probiotic treatment restored TjP1 and ATHO1 to normal levels. The cytokine IL-6 increased in the ACD group compared to naïve mice, whereas IL-10 decreased; probiotic treatment also restored these levels. Intestinal mucus production, affected by ACD, was partially restored by probiotic treatment. The findings suggest that probiotics could be a therapeutic strategy to prevent intestinal issues caused by skin diseases.

Early-life gut microbiota metabolites profoundly influence gut homeostasis, neurodevelopment, metabolic regulation, and immune system maturation. However, there is still a lack of comprehensive summaries and discussions regarding gut microbiota metabolites during early-life stages. This review systematically analyzes microbiota metabolites, including short-chain fatty acids, secondary bile acids, tryptophan metabolites, and branched-chain fatty acids, and delves into their production mechanisms and temporal dynamics. Additionally, the review highlights how maternal factors, breastfeeding, complementary feeding, and environmental influences shape the composition and metabolic functions of the early-life gut microbiota, emphasizing that early life is a crucial window for lifelong health interventions. By integrating the latest research findings and identifying knowledge gaps, this review emphasizes the molecular mechanisms of gut microbiota metabolites and their role in addressing common early-life diseases, including their potential as early biomarkers for screening, prevention, improvement, and even treatment of early diseases, as well as predicting their potential related diseases. On the basis of these insights, this review lays the foundation for future research and practical applications, aiming to promote optimal health from infancy to childhood.

Perioperative neurocognitive disorders (PND), characterized by persistent cognitive impairment lasting from days to years, present substantial clinical challenges in elderly surgical populations, profoundly compromising functional independence, quality of life, and long-term prognosis. We aimed to investigate the effects of short-chain fatty acids (SCFAs) treatment on PND via mediating Brain-derived neurotrophic factor (BDNF)/Phosphatidylinositol3-kinase (PI3K)/Protein kinase B (Akt) pathway. Using 16S rDNA sequencing targeting the V3-V4 hypervariable regions, we first demonstrated significant gut microbiota dysbiosis in PND model rats, accompanied by altered SCFAs profiles. Subsequent fecal microbiota transplantation (FMT) experiments established causal relationships between PND-associated microbial alterations and spatial cognitive deficits. Mechanistically, SCFAs supplementation attenuated neuronal damage and restored synaptic plasticity, as evidenced by Nissl staining quantification (reduced chromatolysis), TUNEL assay (decreased apoptosis rate), and immunohistochemical analysis (upregulated NeuN expression). Molecular investigations revealed that SCFAs-mediated cognitive improvement involved BDNF upregulation and subsequent PI3K/Akt pathway activation, ultimately enhancing neuronal survival and synaptic integrity. Notably, PND animals exhibited characteristic neuropathological features including synaptic density reduction (PSD-95 downregulation), neuroinflammation amplification (IL-6 elevation), and apoptosis activation-all significantly reversed by SCFA intervention. Our findings establish a novel gut-brain axis mechanism wherein microbiota-derived SCFAs may exert neuroprotection through BDNF-dependent PI3K/Akt signaling, and offer potential therapeutic strategies for PND management.

Inulin, a health-promoting dietary fiber, is efficiently metabolized by Weissella paramesenteroides YT175, a beneficial bacterium. The strain demonstrated a diauxic growth pattern within 48 h, reaching an optical density at 600 nm (OD600 nm) of approximately 1.5, accompanied by a significant decrease in pH to around 4.90. Thin-layer chromatography (TLC) analysis reveals an initial preference for inulin oligomers with lower degrees of polymerization (DP). Genomic sequence analysis identified a gene cluster, the pts1BCA operon, associated with inulin metabolism, which includes genes encoding sugar transport proteins, a beta-fructofuranosidase enzyme belonging to the glycoside hydrolase family 32 (GH32), and a transcriptional regulator. Comparative transcriptomic analysis revealed significant upregulation of genes encoding beta-fructofuranosidase, phosphotransferase system (PTS), major facilitator superfamily (MFS), and ATP-binding cassette (ABC) transporters, with qRT-PCR results validating the RNA-Seq data, underscoring their involvement in inulin metabolism. These findings propose a metabolic pathway for the strategic utilization of inulin by YT175, highlighting the synergistic role of its three types of membrane transport proteins in the consumption of inulin oligomers with diverse DPs and its diauxic growth behavior. These insights enhance our understanding of the interaction between probiotics and dietary fibers and pave the way for the development of novel synbiotic foods.

Precision probiotics have shown great promise as novel therapies but have not been fully realized. One major obstacle is that different strains of the same gut microbiota species can induce markedly variable phenotypic outcomes. Here, we aimed to optimize and validate in a preclinical model, a six-species precision probiotic therapy for graft-versus-host disease (GVHD), an autoimmune complication following allogeneic stem cell transplantation. We had identified these six species as associated with protection against GVHD in a prior clinical study. We isolated strains of three of the targeted taxa (B. longum, C. bolteae, and Blautia spp.) from human stem cell transplant patients and characterized their SCFA production in vitro. We observed significant strain-to-strain variability among these gut microbiota taxa in their capacity to produce short-chain fatty acids, a microbiota-derived metabolite shown to be important for mitigating gut GVHD and inflammatory bowel disease, in vitro. We found that B. longum was able to augment butyrate production by C. bolteae and Blautia when co-cultured in vitro. "Optimized" precision probiotics mitigated GVHD and significantly increased survival (p = 0.013, log-rank test) in mice compared to a "standard" probiotic consortium of the same bacterial species obtained from a commercial repository. Importantly, the optimized probiotics resulted in significant increases in intestinal short-chain fatty acid concentrations compared to standard probiotics (p < 0.001, Mann-Whitney test). Our findings highlight the promising potential of utilizing an optimized precision probiotic approach to maximize therapeutic efficacy.

Perioperative neurocognitive disorders (PND) is one of the most common postoperative complications, which can lead to a harmful impact on self-dependence, longer hospital stays, increased medical costs, morbidity, and mortality amongst older adults. Microglia can modulate synapse elimination involved in the complement component protein 1q (C1q) pathway to induce cognitive dysfunction, which is significantly improved by short chain fatty acids (SCFAs) treatment. Here we investigate the effects of SCFAs treatment on PND via mediating C1q complement pathway. High-throughput sequencing of 16S rDNA from fecal samples of male SD rats was applied to assess the changes in gut microbiota. Fecal microbiota transplantation (FMT) was performed to investigate whether gut microbiota from PND rats could alter cognitive impairment. The blood from the rat tail vein was collected to measure the SCFAs concentrations. Hippocampal and brain tissue samples were obtained to perform Western blots, Golgi and immunofluorescence staining. Primary microglia treated with SCFAs or Histone deacetylase inhibitor were cultured to measure microglial activation states and the expression of acetylated histone. The 16S rDNA sequencing results showed that PND rats had the significant changes in the species diversity of the gut microbiota and the metabolite of specifc species. Gut microbiota from PND rats could alter spatial learning and memory, and meanwhile, the changed SCFAs concentrations in plasma were involved. The synapse elimination in PND rats was strikingly reversed by SCFAs treatment involved in modulation complement C1q via suppressing neuroinflammation. This suggests that a link between gut microbiota dysbiosis and cognitive function impairment is involved in synapse elimination via mediating complement C1q pathway. SCFAs treatment can alleviate PND, the mechanisms of which may be associated with regulating complement C1q pathway.

High rehydration beverage consumption represents a significant opportunity for the integration of biotic products that offer the potential to improve body composition and intestinal health. Quercus sideroxyla (IQS) infusions contain polyphenolic compounds with antioxidant and anti-inflammatory properties, and in combination with probiotic strains and prebiotic materials, they offer a promising alternative for generating designer beverages for physically active people. These beverages were formulated using a combination of IQS, agave fructooligosaccharides (FOS), microencapsulated probiotics of Akkermansia muciniphila and Bifidobacterium longum, electrolytes, and glucose. Stable microencapsulated probiotics were obtained by spray drying, using agave gums (PD > 10) and gum arabic as wall materials. The beverage formulations were generated with different percentages of FOS (A:1.6%, B:1.2%, and C:0.8%). The phenolic profile of the beverages was determined by LC-MS/MS, indicating a difference in the concentration of compounds, highlighting changes associated with the addition of FOS compared with IQS. Sensory analyses indicate a preference for the beverage with the highest FOS concentration. The antioxidant potential of the formulations, determined by ABTS, DPPH, and ORAC, showed no differences between the drinks; however, analyses indicate a positive correlation with quinic acid, t-cinnamic acid, quercetin 3-O-glucoside, and total phenolic content, suggesting a synergistic effect. The drinks with higher FOS content exhibited a higher anti-inflammatory potential (EMA). Therefore, it can be concluded that a rehydrating drink with a higher FOS content offers a prebiotic effect with potential anti-inflammatory activity and, according to the panelists, is a suitable drink for evaluating its effects on body composition and intestinal health in people who have recently started physical activity.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by neurodegeneration, axonal damage, demyelination, and inflammation. Recently, gut dysbiosis has been linked to MS and other autoimmune conditions. Namely, gut microbiota has a vital role in regulating immune function by influencing immune cell development, cytokine production, and intestinal barrier integrity. While balanced microbiota fosters immune tolerance, dysbiosis disrupts immune regulation, damages intestinal permeability, and heightens the risk of autoimmune diseases. The critical factor in shaping the gut microbiota and modulating immune response is diet. Research shows that high-fat diets rich in saturated fats are associated with disease progression. Conversely, diets rich in fruits, yogurt, and legumes may lower the risk of MS onset and progression. Specific dietary interventions, such as the Mediterranean diet (MD) and ketogenic diet, have shown potential to reduce inflammation, support neuroprotection, and promote CNS repair. Probiotics, by restoring microbial balance, may also help mitigate immune dysfunction noted in MS. Personalized dietary strategies targeting the gut microbiota hold promise for managing MS by modulating immune responses and slowing disease progression. Optimizing nutrient intake and adopting anti-inflammatory diets could improve disease control and quality of life. Understanding gut-immune interactions is essential for developing tailored nutritional therapies for MS patients.

In this chapter, we update our 2004 review of "The Life of Commensal Escherichia coli in the Mammalian Intestine" (https://doi.org/10.1128/ecosalplus.8.3.1.2), with a change of title that reflects the current focus on "Nutrition of E. coli within the Intestinal Microbiome." The earlier part of the previous two decades saw incremental improvements in understanding the carbon and energy sources that E. coli and Salmonella use to support intestinal colonization. Along with these investigations of electron donors came a better understanding of the electron acceptors that support the respiration of these facultative anaerobes in the gastrointestinal tract. Hundreds of recent papers add to what was known about the nutrition of commensal and pathogenic enteric bacteria. The fact that each biotype or pathotype grows on a different subset of the available nutrients suggested a mechanism for succession of commensal colonizers and invasion by enteric pathogens. Competition for nutrients in the intestine has also come to be recognized as one basis for colonization resistance, in which colonized strain(s) prevent colonization by a challenger. In the past decade, detailed investigations of fiber- and mucin-degrading anaerobes added greatly to our understanding of how complex polysaccharides support the hundreds of intestinal microbiome species. It is now clear that facultative anaerobes, which usually cannot degrade complex polysaccharides, live in symbiosis with the anaerobic degraders. This concept led to the "restaurant hypothesis," which emphasizes that facultative bacteria, such as E. coli, colonize the intestine as members of mixed biofilms and obtain the sugars they need for growth locally through cross-feeding from polysaccharide-degrading anaerobes. Each restaurant represents an intestinal niche. Competition for those niches determines whether or not invaders are able to overcome colonization resistance and become established. Topics centered on the nutritional basis of intestinal colonization and gastrointestinal health are explored here in detail.

With the advancement of metagenomics and metabolomics techniques, the crucial role of the gut microbiome in intestinal, cardiovascular, and metabolic disorders has been extensively explored. Vascular calcification (VC) is common in atherosclerosis, hypertension, diabetes mellitus, and chronic kidney disease. Moreover, it is a significant cause of cardiovascular diseases and mortality. Roseburia intestinalis, as a promising candidate for the next generation of probiotics, plays a substantial role in inhibiting the systemic inflammatory response and holds great potential in the treatment of intestinal diseases, cardiovascular diseases, and metabolic disorders. Its primary metabolite, butyrate, acts on specific receptors (GPR43, GPR41, GPR109a). It enters cells via transporters (MCT1, SMCT1), affecting gene expression through HDACs, PPARγ and Nrf2, promoting energy metabolism and changing the concentration of other metabolites (including AGEs, LPS, BHB) in the circulation to affect the body's life activities. In this paper, we focus on the possible mechanism of the primary metabolite butyrate of Roseburia intestinalis in inhibiting VC, which may become a potential therapeutic target for the treatment of VC and the ways to enhance its effect.

Ruminants release enteric methane into the atmosphere, significantly increasing greenhouse gas emissions and degrading the environment. A common focus of traditional mitigation efforts is on dietary management and manipulation, which may have limits in sustainability and efficacy, exploring the potential of essential microorganisms as a novel way to reduce intestinal methane emissions in ruminants; a topic that has garnered increased attention in recent years. Fermentation and feed digestion are significantly aided by essential microbes found in the rumen, such as bacteria, fungi, and archaea. The practical implications of the findings reported in various studies conducted on rumen gut concerning methane emissions may pave the way to understanding the mechanisms of CH4 production in the rumen to enhance cattle feed efficiency and mitigate CH4 emissions from livestock. This review discussed using essential bacteria to reduce intestinal methane emissions in ruminants. It investigates how particular microbial strains or consortia can alter rumen fermentation pathways to lower methane output while preserving the health and productivity of animals. We also describe the role of probiotics and prebiotics in managing methane emissions using microbial feed additives. Further, recent studies involving microbial interventions have been discussed. The use of new methods involving functional metagenomics and meta-transcriptomics for exploring the rumen microbiome structure has been highlighted. This review also emphasizes the challenges faced in altering the gut microbiome and future directions in this area.

Type II diabetes mellitus (T2DM) has experienced a dramatic increase globally across countries of various income levels over the past three decades. The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors. While numerous pharmaceutical therapies have been developed, there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects. In this context, the exploration of the gut microbiome presents a promising avenue. Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals, suggesting its potential role in the disease's pathogenesis and progression. This emerging field offers diverse applications, particularly in modifying the gut environment through the administration of prebiotics, probiotics, and fecal microbiome transfer. These inter-ventions aim to restore a healthy microbiome balance, which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM. Although current results from clinical trials have not yet shown dramatic effects on diabetes management, the groundwork has been laid for deeper investigation. Ongoing and future clinical trials are critical to advancing our understanding of the microbiome's impact on diabetes. By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism, researchers can develop more targeted interventions. The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM, potentially reducing the disease's burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic, systemic health improvements.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), the facilitation of short-chain fatty acids' (SCFAs) production, and the activation of glucagon-like peptide-1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we discuss research in other disease models that have used probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

The short-chain fatty acids (SCFAs) butyrate, propionate and acetate are microbial metabolites and their availability in the gut and other organs is determined by environmental factors, such as diet and use of antibiotics, that shape the diversity and metabolism of the microbiota. SCFAs regulate epithelial barrier function as well as mucosal and systemic immunity via evolutionary conserved processes that involve G protein-coupled receptor signalling or histone deacetylase activity. Indicatively, the anti-inflammatory role of butyrate is mediated through direct effects on the differentiation of intestinal epithelial cells, phagocytes, B cells and plasma cells, and regulatory and effector T cells. Intestinally derived SCFAs also directly and indirectly affect immunity at extra-intestinal sites, such as the liver, the lungs, the reproductive tract and the brain, and have been implicated in a range of disorders, including infections, intestinal inflammation, autoimmunity, food allergies, asthma and responses to cancer therapies. An ecological understanding of microbial communities and their interrelated metabolic states, as well as the engineering of butyrogenic bacteria may support SCFA-focused interventions for the prevention and treatment of immune-mediated diseases.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)-derived EVs (R-EVs) as potent anti-inflammatory mediators in treating dextran sulfate sodium-induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R-EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R-EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile-Pro-Ile in the vesicular structure, R-EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP-1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.

Throughout the life span of a host, bifidobacteria have shown superior colonization and glycan abilities. Complex glycans, such as human milk oligosaccharides and plant glycans, that reach the colon are directly internalized by the transport system of bifidobacteria, cleaved into simple structures by extracellular glycosyl hydrolase, and transported to cells for fermentation. The glycan utilization of bifidobacteria introduces cross-feeding activities between bifidobacterial strains and other microbiota, which are influenced by host nutrition and regulate gut homeostasis. This review discusses bifidobacterial glycan utilization strategies, focusing on the cross-feeding involved in bifidobacteria and its potential health benefits. Furthermore, the impact of cross-feeding on the gut trophic niche of bifidobacteria and host health is also highlighted. This review provides novel insights into the interactions between microbe-microbe and host-microbe.

The gut microbiota is widely acknowledged as a crucial factor in regulating host health. The structure of dietary fibers determines changes in the gut microbiota and metabolic differences resulting from their fermentation, which in turn affect gut microbe-related health effects. β-Glucan (BG) is a widely accessible dietary fiber to humans, and its structural characteristics vary depending on the source. However, the interactions between different structural BGs and gut microbiota remain unclear. This study used an in vitro fermentation model to investigate the effects of BG on gut microbiota, and microbiomics and metabolomics techniques to explore the relationship between the structure of BG, bacterial communities, and metabolic profiles. The four sources of BG (barley, yeast, algae, and microbial fermentation) contained different types and proportions of glycosidic bonds, which differentially altered the bacterial community. The BG from algal sources, which contained only β(1 → 4) glycosidic bonds, was the least metabolized by the gut microbiota and caused limited metabolic changes. The other three BGs contain more diverse glycosidic bonds and can be degraded by bacteria from multiple genera, causing a wider range of metabolic changes. This work also suggested potential synergistic degradation relationships between gut bacteria based on BG. Overall, this study deepens the structural characterization-microbial-functional understanding of BGs and provides theoretical support for the development of gut microbiota-targeted foods.

Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.

The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications.

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

Palmitoleic acid (POA) is an omega-7 monounsaturated fatty acid that has been suggested to improve metabolic disorders. However, it remains unclear whether gut microbiota plays a role in the amelioration of metabolic disorders by POA. This study aims to investigate the regulation of POA on metabolism, as well as systemic inflammation in HFD-fed mice from the perspective of serum metabolome and gut microbiome.

Thirty-six C57BL/6 male mice are randomly assigned to either a normal chow diet containing 1.9% w/w lard or an HFD containing 20.68% w/w lard or 20.68% w/w sea buckthorn pulp oil for 16 weeks. The study finds that POA significantly attenuated hyperlipidemia, insulin resistance, and inflammation in HFD-fed mice. POA supplementation significantly alters the composition of serum metabolites, particularly lipid metabolites in the glycerophospholipid metabolism pathway. POA obviously increases the abundance of Bifidobacterium and decreases the abundance of Allobaculum. Importantly, the study finds that glycerophosphocholine mediates the effect of Bifidobacterium on LDL-C, sphingomyelin mediates the effect of Bifidobacterium on IL-6, and maslinic acid mediates the effect of Allobaculum on IL-6.

The results suggest that exogenous POA can improve metabolic disorders and inflammation in HFD-fed mice, potentially by modulating the serum metabolome and gut microbiome.

Metabolic-associated liver diseases have emerged pandemically across the globe and are clinically related to metabolic disorders such as obesity and type 2 diabetes. The new nomenclature and definition (i.e. metabolic dysfunction-associated steatotic liver disease - MASLD; metabolic dysfunction-associated steatohepatitis - MASH) reflect the nature of these complex systemic disorders, which are characterized by inflammation, gut dysbiosis and metabolic dysregulation. In this review, we summarize recent advantages in understanding the pathophysiology of MASLD, which we parallel to emerging therapeutic concepts.

We summarize the pathophysiologic concepts of MASLD and its transition to MASH and subsequent advanced sequelae of diseases. Furthermore, we highlight how dietary constituents, microbes and associated metabolites, metabolic perturbations, and immune dysregulation fuel lipotoxicity, hepatic inflammation, liver injury, insulin resistance, and systemic inflammation. Deciphering the intricate pathophysiologic processes that contribute to the development and progression of MASLD is essential to develop targeted therapeutic approaches to combat this escalating burden for health-care systems.

The rapidly increasing prevalence of metabolic dysfunction-associated steatotic liver disease challenges health-care systems worldwide. Understanding pathophysiologic traits is crucial to improve the prevention and treatment of this disorder and to slow progression into advanced sequelae such as cirrhosis and hepatocellular carcinoma.

Postpartum dairy cows can develop nutritional diarrhea when their diet is abruptly changed for milk production. However, it is unclear whether nutritional diarrhea develops as a result of gut acidosis and/or dysbiosis. This study aimed to uncover changes in the gastrointestinal microbiota and its fermentation parameters in response to nutritional diarrhea in postpartum dairy cows. Rumen and fecal samples were collected from twenty-four postpartum cows fed with the same diet but with different fecal scores: the low-fecal-score (LFS: diarrheic) group and high-fecal-score (HFS: non-diarrheic) group. A microbiota difference was only observed for fecal microbiota, with the relative abundance of Defluviitaleaceae_UCG-011 and Lachnospiraceae_UCG-001 tending (p < 0.10) to be higher in HFS cows compared to LFS cows, and Frisingicoccus were only detected in HFS cows. The fecal bacterial community in LFS cows had higher robustness (p < 0.05) compared to that in HFS cows, and also had lower negative cohesion (less competitive behaviors) and higher positive cohesion (more cooperative behaviors) (p < 0.05) compared that in to HFS cows. Lower total volatile fatty acids and higher ammonia nitrogen (p < 0.05) were observed in LFS cows' feces compared to HFS cows. The observed shift in fecal bacterial composition, community networks, and metabolites suggests that hindgut dysbiosis could be related to nutritional diarrhea in postpartum cows.

Bifidobacterium is a widely distributed commensal bacterial genus that displays beneficial pro-homeostatic and anti-inflammatory immunomodulatory properties. Depletion or absence of Bifidobacterium in humans and model organisms is associated with autoimmune responses and impaired immune homeostasis. At the cellular level, Bifidobacterium upregulates suppressive regulatory T cells, maintains intestinal barrier function, modulates dendritic cell and macrophage activity, and dampens intestinal Th2 and Th17 programs. While there has been a large volume of literature characterizing the probiotic properties of various Bifidobacterial species, the likely multifactorial mechanisms underlying these effects remain elusive, in particular, its immune tolerogenic effect. However, recent work has shed light on Bifidobacterium surface structural polysaccharide and protein elements, as well as its metabolic products, as commensal mediators of immune homeostasis. This review aims to discuss several mechanisms Bifidobacterium utilizes for immune modulation as well as their indirect impact on the regulation of gut microbiome structure and function, from structural molecules to produced metabolites. These mechanisms are pertinent to an increasingly networked understanding of immune tolerance and homeostasis in health and disease.

Mushroom dietary fiber is a type of bioactive macromolecule derived from the mycelia, fruiting bodies, or sclerotia of edible or medicinal fungi. The use of mushroom dietary fiber as a prebiotic has recently gained significant attention for providing health benefits to the host by promoting the growth of beneficial microorganisms; therefore, mushroom dietary fiber has promising prospects for application in the functional food industry and in drug development. This review summarizes methods for the preparation and modification of mushroom dietary fiber, its degradation and metabolism in the intestine, its impact on the gut microbiota community, and the generation of short-chain fatty acids (SCFAs); this review also systematically summarizes the beneficial effects of mushroom dietary fiber on host health. Overall, this review aims to provide theoretical guidance and a fresh perspective for the prebiotic application of mushroom dietary fiber in the development of new functional foods and drugs.

In recent years, probiotics have been used in functional gastrointestinal disorders, including chronic constipation (CC). The effect of Bifidobacterium infantis strain 35624 on the gut microbiota of CC patients has not been previously studied. Our aim was to analyze the fecal microbiota of constipated patients, before and after consuming a single-strain probiotic (B. infantis strain 35624).

We used 16S rRNA gene high-throughput sequencing to analyze the fecal microbiota of female patients (n=13) with CC. Patients were instructed to ingest one capsule of Alflorex® (containing 1×109 CFUs/g B. infantis strain 35624) daily for eight weeks. Fecal samples were obtained at the baseline and end (final) of probiotic administration.

Alpha diversity metrics did not differ between the baseline and final periods. The butyrate producer, Oscillospira, was the taxon most strongly correlated with amplicon sequence variants (R2=0.55, p<0.0001). Except for a few bacterial taxa, there were no significant differences in relative abundance between the baseline and final periods. Beta-diversity measures also showed limited evidence for the differences between the two time periods.

The results suggest that the fecal bacterial microbiota remains stable in constipated women consuming a single-strain probiotic. Those findings may be helpful in better understanding probiotic functioning in patients with digestive disorders.

Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome.

Obesity is associated with gastrointestinal (GI) tract and central nervous system (CNS) disorders. High-fat diet (HFD) feeding-induced obesity in mice induces dysbiosis, causing a shift toward bacteria-derived metabolites with detrimental effects on metabolism and inflammation: events often contributing to the onset and progression of both GI and CNS disorders. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with beneficial effects in mouse models of GI and CNS disorders. However, the mechanisms underlining its enteroprotective and neuroprotective effects still need to be fully understood. Here, we aimed to study the effects of PEA on intestinal inflammation and microbiota alterations resulting from lipid overnutrition. Ultramicronized PEA (30 mg/kg/die per os) was administered to HFD-fed mice for 7 weeks starting at the 12th week of HFD regimen. At the termination of the study, the effects of PEA on inflammatory factors and cells, gut microbial features and tryptophan (TRP)-kynurenine metabolism were evaluated. PEA regulates the crosstalk between the host immune system and gut microbiota via rebalancing colonic TRP metabolites. PEA treatment reduced intestinal immune cell recruitment, inflammatory response triggered by HFD feeding, and corticotropin-releasing hormone levels. In particular, PEA modulated HFD-altered TRP metabolism in the colon, rebalancing serotonin (5-HT) turnover and reducing kynurenine levels. These effects were associated with a reshaping of gut microbiota composition through increased butyrate-promoting/producing bacteria, such as Bifidobacterium, Oscillospiraceae and Turicibacter sanguinis, with the latter also described as 5-HT sensor. These data indicate that the rebuilding of gut microbiota following PEA supplementation promotes host 5-HT biosynthesis, which is crucial in regulating intestinal function.

Fibre-based dietary interventions are at the forefront of gut microbiome modulation research, with a wealth of 16S rRNA information to demonstrate the prebiotic effects of isolated fibres. However, there is a distinct lack of data relating to the effect of a combination of soluble and insoluble fibres in a convenient-to-consume fruit juice food matrix on gut microbiota structure, diversity, and function. Here, we aimed to determine the impact of the MOJU Prebiotic Shot, an apple, lemon, ginger, and raspberry fruit juice drink blend containing chicory inulin, baobab, golden kiwi, and green banana powders, on gut microbiota structure and function. Healthy adults (n = 20) were included in a randomised, double-blind, placebo-controlled, cross-over study, receiving 60 mL MOJU Prebiotic Shot or placebo (without the fibre mix) for 3 weeks with a 3-week washout period between interventions. Shotgun metagenomics revealed significant between-group differences in alpha and beta diversity. In addition, the relative abundance of the phyla Actinobacteria and Desulfobacteria was significantly increased as a result of the prebiotic intervention. Nine species were observed to be differentially abundant (uncorrected p-value of <0.05) as a result of the prebiotic treatment. Of these, Bifidobacterium adolescentis and CAG-81 sp900066785 (Lachnospiraceae) were present at increased abundance relative to baseline. Additionally, KEGG analysis showed an increased abundance in pathways associated with arginine biosynthesis and phenylacetate degradation during the prebiotic treatment. Our results show the effects of the daily consumption of 60 mL MOJU Prebiotic Shot for 3 weeks and provide insight into the functional potential of B. adolescentis.

Omnivorous cockroaches host a complex hindgut microbiota comprised of insect-specific lineages related to those found in mammalian omnivores. Many of these organisms have few cultured representatives, thereby limiting our ability to infer the functional capabilities of these microbes. Here we present a unique reference set of 96 high-quality single cell-amplified genomes (SAGs) from bacterial and archaeal cockroach gut symbionts. We additionally generated cockroach hindgut metagenomic and metatranscriptomic sequence libraries and mapped them to our SAGs. By combining these datasets, we are able to perform an in-depth phylogenetic and functional analysis to evaluate the abundance and activities of the taxa in vivo. Recovered lineages include key genera within Bacteroidota, including polysaccharide-degrading taxa from the genera Bacteroides, Dysgonomonas, and Parabacteroides, as well as a group of unclassified insect-associated Bacteroidales. We also recovered a phylogenetically diverse set of Firmicutes exhibiting a wide range of metabolic capabilities, including-but not limited to-polysaccharide and polypeptide degradation. Other functional groups exhibiting high relative activity in the metatranscriptomic dataset include multiple putative sulfate reducers belonging to families in the Desulfobacterota phylum and two groups of methanogenic archaea. Together, this work provides a valuable reference set with new insights into the functional specializations of insect gut symbionts and frames future studies of cockroach hindgut metabolism.

The human gut is home to trillions of microorganisms that influence several aspects of our health. This dense microbial community targets almost all dietary polysaccharides and releases multiple metabolites, some of which have physiological effects on the host. A healthy equilibrium between members of the gut microbiota, its microbial diversity, and their metabolites is required for intestinal health, promoting regulatory or anti-inflammatory immune responses. In contrast, the loss of this equilibrium due to antibiotics, low fiber intake, or other conditions results in alterations in gut microbiota composition, a term known as gut dysbiosis. This dysbiosis can be characterized by a reduction in health-associated microorganisms, such as butyrate-producing bacteria, enrichment of a small number of opportunistic pathogens, or a reduction in microbial diversity. Bifidobacterium species are key species in the gut microbiome, serving as primary degraders and contributing to a balanced gut environment in various ways. Colonization resistance is a fundamental property of gut microbiota for the prevention and control of infections. This community competes strongly with foreign microorganisms, such as gastrointestinal pathogens, antibiotic-resistant bacteria, or even probiotics. Resistance to colonization is based on microbial interactions such as metabolic cross-feeding, competition for nutrients, or antimicrobial-based inhibition. These interactions are mediated by metabolites and metabolic pathways, representing the inner workings of the gut microbiota, and play a protective role through colonization resistance. This review presents a rationale for how microbial interactions provide resistance to colonization and gut dysbiosis, highlighting the protective role of Bifidobacterium species.

Aim: The human gut Bifidobacterium community has been studied in detail in infants and following dietary interventions in adults. However, the variability of the distribution of Bifidobacterium species and intra-species functions have been little studied, particularly beyond infancy. Here, we explore the ecology of Bifidobacterium communities in a large public dataset of human gut metagenomes, mostly corresponding to adults. Methods: We selected 9.515 unique gut metagenomes from curatedMetagenomicData. Samples were partitioned by applying Dirichlet's multinomial mixture to Bifidobacterium species. A functional analysis was performed on > 2.000 human-associated Bifidobacterium metagenome-assembled genomes (MAGs) paired with participant gut microbiome and health features. Results: We identified several Bifidobacterium-based partitions in the human gut microbiome differing in terms of the presence and abundance of Bifidobacterium species. The partitions enriched in both B. longum and B. adolescentis were associated with gut microbiome diversity and a higher abundance of butyrate producers and were more prevalent in healthy individuals. B. bifidum MAGs harboring a set of genes potentially related to phages were more prevalent in partitions associated with a lower gut microbiome diversity and were genetically more closely related. Conclusion: This study expands our knowledge of the ecology and variability of the Bifidobacterium community, particularly in adults, and its specific association with the gut microbiota and health. Its findings may guide the rational selection of Bifidobacterium strains for gut microbiome complementation according to the individual's endogenous Bifidobacterium community. Our results also suggest that gut microbiome stratification for particular genera may be relevant for studies of variations of species and associations with the gut microbiome and health.

Human gut microbiota species which are next-generation probiotics (NGPs) candidates are of high interest as they have shown the potential to treat intestinal inflammation and other diseases. Unfortunately, these species are often not robust enough for large-scale cultivation, especially in maintaining diversity in co-culture production.

In this study, we describe interactions between human gut microbiota species in the cultivation process with unique substrates. We also demonstrated that it is possible to change the species ratio in co-culture by changing the ratio of carbon sources.

We screened 25 different bacterial species based on their metabolic capabilities. After evaluating unique substrate possibilities, we chose Anaerostipes caccae (A. caccae), Bacteroides thetaiotaomicron (B. thetaiotaomicron), and Bacteroides vulgatus (B. vulgatus) as subjects for further study. D-sorbitol, D-xylose, and D-galacturonic acid were selected as substrates for A. caccae, B. thetaiotaomicron, and B. vulgatus respectively. All three species were cultivated as both monocultures and in co-cultures in serial batch fermentations in an isothermal microcalorimeter.

Positive interactions were detected between the species in both co-cultures (A. caccae + B. thetaiotaomicron; A. caccae + B. vulgatus) resulting in higher heat production compared to the sum of the monocultures. The same positive cross-feeding interactions took place in larger-scale cultivation experiments. We confirmed acetate and lactate cross-feeding between A. caccae and B. thetaiotaomicron with flux balance analysis (FBA).

Changing the ratio of the selected carbon sources in the medium changed the species ratio accordingly. Such robustness is the basis for developing more efficient industrial co-culture processes including the production of NGPs.

Microbiome-targeting therapies have received great attention as approaches to prevent disease in infants born preterm, but their safety and efficacy remain uncertain. Here we summarize the existing literature, focusing on recent meta-analyses and systematic reviews that evaluate the performance of probiotics, prebiotics, and/or synbiotics in clinical trials and studies, emphasizing interventions for which the primary or secondary outcomes were prevention of necrotizing enterocolitis, late-onset sepsis, feeding intolerance, and/or reduction in hospitalization length or all-cause mortality. Current evidence suggests that probiotics and prebiotics are largely safe but conclusions regarding their effectiveness in the neonatal intensive care unit have been mixed. To address this ambiguity, we evaluated publications that collectively support benefits of probiotics with moderate to high certainty evidence in a recent comprehensive network meta-analysis, highlighting limitations in these trials that make it difficult to support with confidence the routine, universal administration of probiotics to preterm infants.

Bifidobacterium longum BB536 supplementation can be used to regulate bowel movements in various people, including healthy subjects and patients with irritable bowel syndrome (IBS); however, individuals vary in their responses to B. longum BB536 treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates the effects of diet or drugs on the host. Here, we investigated intestinal features, such as the microbiome and metabolome, related to B. longum BB536 effectiveness in increasing bowel movement frequency.

A randomized, double-blind controlled crossover trial was conducted with 24 adults who mainly tended to be constipated. The subjects received a two-week dietary intervention consisting of B. longum BB536 in acid-resistant seamless capsules or similarly encapsulated starch powder as the placebo control. Bowel movement frequency was recorded daily, and fecal samples were collected at several time points, and analyzed by metabologenomic approach that consists of an integrated analysis of metabolome data obtained using mass spectrometry and microbiome data obtained using high-throughput sequencing. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predicted by machine learning based on the microbiome and metabolome features of the fecal samples collected before B. longum intake. The abundances of eight bacterial genera were significantly different between responders and nonresponders.

Intestinal microbiome and metabolome profiles might be utilized as potential markers of improved bowel movement after B. longum BB536 supplementation. These findings have implications for the development of personalized probiotic treatments.