Gut Function Research Articles

How Do Cyclodextrins and Dextrans Affect the Gut Microbiome? Review of Prebiotic Activity

The modulation of the gut microbiome through dietary components has garnered significant attention for its potential health benefits. Prebiotics, non-digestible food ingredients that promote the growth of beneficial gut bacteria, play a crucial role in maintaining gut health, enhancing immune function, and potentially preventing various metabolic and inflammatory disorders. This review explores the prebiotic activity of cyclodextrins and dextrans, focusing on their ability to influence gut microbiota composition and function. Both cyclodextrins and dextrans have demonstrated the capacity to promote the growth of beneficial bacterial populations, while also impacting short-chain fatty acid production, crucial for gut health.

Child health, nutrition and gut microbiota development during the first two years of life; study protocol of a prospective cohort study from the Khyber Pakhtunkhwa, Pakistan

Recent evidence suggests that the development of gut microbiota during infancy affects several metabolic, immune, and endocrine pathways in humans. An imbalance in gut microbiota diversity or function, also known as dysbiosis, not only affects early child growth and development, but is also linked with the development of chronic, non-communicable diseases in later life. The Child Health And Microbiome Development Study – Pakistan (CHAMP) study aimed to longitudinally assess gut microbiota development and associated factors (maternal, child, and demographic) during early childhood in populations residing in malnutrition-endemic communities in Pakistan. A prospective cohort of mother-infant pairs (n=70) will be recruited from District Swat, Pakistan, and followed for two years. Complete information about demographic characteristics, anti-natal and post-natal care, dietary intake, feeding practices, and child health will be collected at baseline and 3, 6, 12, 18, and 24 months. Anthropometric measurements (height, weight, mid-upper arm circumference, and head circumference), dry blood spots, and fecal samples were also collected. Ethical approval for the study was obtained from Khyber Medical University, Pakistan. The study is also registered on clincaltrial.gov (Ref no: NCT05793294). The study findings will help researchers understand gut microbiota development, associated factors, and their impact on longitudinal growth in infants during the first two years of life.

Metagenomics reveals the divergence of gut microbiome composition and function in two common pika species (Ochotona curzoniae, Ochotona daurica) in China.

Gut microbiome plays crucial roles in animal adaptation and evolution. However, research on adaptation and evolution of small wild high-altitude mammals from the perspective of gut microbiome is still limited. In this study, we compared difference in intestinal microbiota composition and function in Plateau pikas (Ochotona curzoniae) and Daurian pikas (Ochotona daurica) using metagenomic sequencing. Our results showed that microbial community structure had distinct differences in different pika species. Prevotella, Methanosarcina, Rhizophagus and Podoviridae were abundant bacteria, archaea, eukaryotes and viruses in Plateau pikas, respectively. However, Prevotella, Methanosarcina, Ustilago and Retroviridae were dominated in Daurian pikas. Functional pathways related to carbohydrate metabolism that refer to utilization of pectin, hemicellulose and debranching enzymes were abundant in Plateau pikas, while the function for degradation of chitin, lignin and cellulose was more concentrated in Daurian pikas. Pika gut had abundant multidrug resistance genes, followed by glycopeptide and beta-lactamase resistance genes, as well as high-risk ARGs, such as mepA, tetM and bacA. Escherichia coli and Klebsiella pneumoniae may be potential hosts of mepA. This research provided new insights for adaptation and evolution of wild animals from perspective of gut microbiome, and broadened our understanding of high-risk ARGs and potential pathogens of wild animals.

Functional analysis of antigen presentation by enteric glial cells during intestinal inflammation.

The Enteric Nervous System is composed of a vastly interconnected network of neurons and glial cells that coordinate to regulate homeostatic gut function including intestinal motility, nutrient sensing, and mucosal barrier immunity. Enteric Glial Cells (EGCs) are a heterogeneous cell population located throughout the gastrointestinal tract and have well described roles in regulating intestinal immune responses. Enteric Glial Cells have been suggested to act as nonconventional antigen presenting cells via the Major Histocompatibility Complex II (MHC II), though this has not been confirmed functionally. Here, we investigate the capability of EGCs to present antigen on MHC I and MHC II using in vitro antigen presentation assays performed with primary murine EGC cultures. We found that EGCs are capable of functional antigen presentation on MHC I, including antigen cross-presentation, but are not capable of functional antigen presentation on MHC II. We also determined EGC cell surface MHC I and MHC II expression levels by flow cytometry during intestinal inflammation during Dextran Sodium Sulfate-induced colitis or acute Toxoplasma gondii infection. We found that EGCs upregulate MHC I during acute T. gondii infection and induce low-level MHC II expression. These findings suggest that EGCs may be important in the regulation of CD8+ T cell responses via MHC I mediated antigen (cross) presentation but may not be relevant for MHC II-mediated antigen presentation.

Strategic alteration of arabinoxylan feruloylation enables selective shaping of the human gut microbiota

Arabinoxylans (AXs) are promising prebiotic candidates abundant in cereals. While AX feruloylation impacts properties, its effects on long chains mimicking native structures are unclear. This study revealed a dose-dependent impact of long chain AX feruloylation on gut microbial composition and function. In vitro fecal fermentation with varying AX feruloylation showed increased Bacteroidetes and propionate along with decreased Firmicutes and butyrate. Distinct Bacteroides populations were enriched under different feruloylation levels, suggesting specialized adaptation. Community dynamics and co-occurrence networks highlighted intricate taxon-specific responses, underscoring the unique microbial profiles shaped by individual variations. This study lays the foundation for elucidating the metabolic pathways and enzymatic machineries enabling utilization of feruloylated AXs based on the dose-dependent enrichment of specific taxa. This knowledge can inform rational design of customized prebiotics through precision nutrition. This work provides novel insights into tailoring cereal biomass fermentation and microbiome structure-function relationships. It establishes a platform for developing optimized feruloylated prebiotics to deliberately modulate gut ecology and address intestinal dysbiosis.

Jianghua Kucha black tea containing theacrine attenuates depression-like behavior in CUMS mice by regulating gut microbiota-brain neurochemicals and cytokines

Theacrine and theaflavins are known for their potential to mitigate depression and cognitive impairment. Jianghua Kucha black tea (JH) contains both compounds, yet its antidepressant properties are seldom documented. This study evaluated the effects of JH on depression in chronic unpredictable mild stress (CUMS) mice and explored the underlying mechanisms through integrative analyses of gut microbiota and fecal metabolomics. JH was found to significantly alleviate CUMS-induced depression-like behavior by improving body weight, food intake, 1% sucrose preference, immobility time, and numbers of crossings and standings compared to Zhuyeqi black tea (ZYQ), which contains theaflavins. JH notably altered the gut microbiota composition, enriching genera such as Turicibacter, Faecalibaculum, Akkermansia, and Desulfovibrio, while inhibiting genera norank_f__Muribaculaceae and Lactobacillus. Additionally, JH modified the fecal metabolite profile, characterized by increased levels of several secondary bile acids (BAs) and decreased levels of several purine intermediate metabolites. Furthermore, JH upregulated levels of monoamine neurotransmitters (5-HT and DA) and brain-derived neurotrophic factor (BDNF), while downregulating pro-inflammatory cytokines IL-6 and TNF-α in brain tissue. These findings suggested that JH could mitigate CUMS-induced depression-like behavior, potentially by modulating gut microbiota composition and function, as well as brain neurochemicals and cytokines.

Impact of maternal high-fat diet on offspring gut microbiota during short-term high-fat diet exposure in mice.

Alterations in the gut microbiome have been linked to obesity, with maternal high-fat diet (HF) playing a role in shaping offspring microbiome composition. However, the sex-specific responses to maternal HF diet and the impact of subsequent dietary challenges remain unclear. This study investigated the effects of maternal HF diet on offspring gut microbiota structure and predicted functional profile in response to short-term postnatal HF diet exposure with a focus on sex-specific responses. Female and male offspring of maternal control (C) diet or maternal HF diet were weaned onto C diet or HF diet. Offspring were euthanized at 13 weeks of age and cecal contents were collected for bacterial taxonomic profiling. Maternal HF diet reduced α-diversity, notably in male offspring weaned onto HF diet. Sex-specific differences were observed in the gut microbial composition and predicted functional potential. Furthermore, the influence of maternal diet on bacterial community structure and functional potential varied depending on postnatal diet. Maternal HF diet led to increased relative abundance of Corynebacterium in female offspring and decreased abundance of Akkermansia and Roseburia in male offspring. These findings underscore the sexually dimorphic nature of maternal HF diet effects on gut microbiota composition and function, with implications for developmental programming and metabolic health.

Changes in intestinal flora associated with childhood sleep-disordered breathing and the pathogenesis of non-alcoholic fatty liver disease in children

Objective:To explore the interaction between pediatric sleep-disordered breathing（SDB）, the intestinal microbiota, and pediatric non-alcoholic fatty liver disease（NAFLD）. Methods:A total of 63 non-obese children（47 children with SDB in the experimental group and 16 without SDB in the control group） were enrolled in this study. The liver function and degree of SDB were assessed in both groups. High-throughput 16S rRNA sequencing was conducted to detect the composition and functional variations of the intestinal microbiota in the two groups of children. Results:Compared with children in the experimental group, serum ALT and AST levels were higher in the control group. and the relative proteobacteria abundance of intestinal flora increased, and the relative abundance of Bacteroidetes decreased significantly. Function including membrane transport, carbohydrate metabolism and lipid metabolism, were enriched in the intestinal microbiota of children with SDB. Conclusion:The composition and functional annotation of the pediatric liver functional status and gut microbiota were significantly different between the two groups of children with and without SDB. Changes in SDB-associated intestinal bacterial abundance may be related to the pathogenesis of pediatric NAFLD.

Physiopathological Roles of White Adiposity and Gut Functions in Neuroinflammation.

White adipose tissue (WAT) and the gut are involved in the development of neuroinflammation when an organism detects any kind of injury, thereby triggering metainflammation. In fact, the autonomous nervous system innervates both tissues, although the complex role played by the integrated sympathetic, parasympathetic, and enteric nervous system functions have not been fully elucidated. Our aims were to investigate the participation of inflamed WAT and the gut in neuroinflammation. Firstly, we conducted an analysis into how inflamed peripheral WAT plays a key role in the triggering of metainflammation. Indeed, this included the impact of the development of local insulin resistance and its metabolic consequences, a serious hypothalamic dysfunction that promotes neurodegeneration. Then, we analyzed the gut-brain axis dysfunction involved in neuroinflammation by examining cell interactions, soluble factors, the sensing of microbes, and the role of dysbiosis-related mechanisms (intestinal microbiota and mucosal barriers) affecting brain functions. Finally, we targeted the physiological crosstalk between cells of the brain-WAT-gut axis that restores normal tissue homeostasis after injury. We concluded the following: because any injury can result not only in overall insulin resistance and dysbiosis, which in turn can impact upon the brain, but that a high-risk of the development of neuroinflammation-induced neurodegenerative disorder can also be triggered. Thus, it is imperative to avoid early metainflammation by applying appropriate preventive (e.g., lifestyle and diet) or pharmacological treatments to cope with allostasis and thus promote health homeostasis.

Effects of Limosilactobacillus reuteri DSM 17938 in neonates exposed to antibiotics: a randomised controlled trial.

Perinatal antibiotic exposure potentially leads to gut microbiota dysbiosis, which is associated with functional gastrointestinal disorders (FGIDs). We aimed to investigate the effects of Limosilactobacillus reuteri DSM 17938 supplementation on the development of FGIDs, crying and sleep duration, and the gut microbial composition in infants exposed to antibiotics during the neonatal period. In this randomised, double-blind, placebo-controlled study, we included 89 term neonates treated with antibiotics. Neonates received the study product for six weeks. FGIDs, assessed by the Infant Gastrointestinal Symptom Questionnaire, crying and sleep duration were assessed at four and eight weeks, and six months after enrolment. Faecal samples were collected six weeks and twelve months after enrolment. The gut microbial community composition was analysed using 16S amplicon sequencing and qPCR. The proportion of infants with FGIDs was greater in the control group, although the difference between the groups was significant only six months after enrolment. At all time points, the probiotic group presented a longer sleep duration and shorter crying time than the control group, but the difference was not statistically significant. Probiotic consumption had no significant effect on the gut microbiota composition except for increased L. reuteri DSM 17938 abundance in the probiotic group at six weeks after enrolment. At specific time points after supplementation with L. reuteri DSM 17938, a reduction in the prevalence of FGIDs was observed in the probiotic group. However, no observable effect on the gut microbiota was detected during the intervention. We believe that probiotic supplementation in neonates during and after antibiotic treatment to minimise the negative effects of antibiotics on gut function during this vulnerable period of human development warrants further investigation. The trial is registered at ClinicalTrials.gov (NCT02865564).

Mitigating Dietary Bisphenol Exposure Through the Gut Microbiota: The Role of Next-Generation Probiotics in Bacterial Detoxification.

Bisphenols, such as bisphenol A and its analogs, which include bisphenol S, bisphenol F, bisphenol AF, and tetramethyl bisphenol F, are chemical contaminants commonly found in food that raise serious health concerns. These xenobiotics can potentially have harmful effects on human health. The gut microbiota plays a crucial role in metabolizing and neutralizing these substances, which is essential for their detoxification and elimination. Probiotic supplementation has been studied for its ability to modulate the gut microbiota's composition and function, enhancing detoxification processes. Next-Generation Probiotics (NGPs) may exhibit better properties than traditional strains and are designed for targeted action on specific conditions, such as obesity. By modulating inflammatory responses and reducing the secretion of pro-inflammatory cytokines, they can significantly improve host health. Research on NGPs' ability to neutralize obesogenic bisphenols remains limited, but their potential makes this a promising area for future exploration. This review aims to understand the mechanisms of the chemical transformation of bisphenol through its interactions with the gut microbiota and the role of probiotics, particularly NGPs, in these processes. Understanding the interplay between bisphenols, gut microbiota, and NGPs may pave the way for strategies to counteract the negative health effects associated with daily and chronic exposure to bisphenols, which is crucial for food safety and consumer health protection.

Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.

Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD). In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial. Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II. FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.

Associations between Gut Microbiota and Microbial Metabolites in Adjuvant- induced Arthritis Rats with Moist Heat Arthralgia Spasm Syndrome.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. According to Traditional Chinese Medicine (TCM) syndromes theory, moist heat arthralgia spasm syndrome is the most prevalent syndrome of RA patients in the active period. However, the mechanism of alteration of gut microbiota in RA with moist heat arthralgia spasm syndrome has not been reported until now. This study focused on the alteration of gut microbiota in adjuvant-induced arthritis rats with moist heat arthralgia spasm syndrome, elaborated its regulation mechanism, and analyzed the associations between gut microbiota and microbial metabolites. The disease-syndrome combination rat model of RA with moist heat arthralgia spasm syndrome was constructed with Adjuvant-Induced Arthritis (AIA) under damp-heat stimulating. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure serum biochemical indicators. Damages of ankle joints were observed using hematoxylin and eosin (H&E). 16 small ribosomal subunit RNA (16S rRNA) gene sequencing was conducted to assess the gut microbiota composition and function on feces from rats. Alterations in fecal metabolites profiling were evaluated by fecal metabolomics through Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS). Pearson correlation analysis was performed to explore the associations of altered gut microbiota and microbial metabolites in Model rats. The imbalance of gut microbiota in Model rats was accompanied by metabolic disorders. Lactobacillus, Prevotellaceae_NK3B31_group, Allobaculum, Prevotellaceae_UCG_001, Alloprevotella, and Dubosiella were found to be dominant genera in Model rats. In total, 357 metabolites were significantly altered in Model rats and predominantly enriched into fatty acid degradation and glycerophospholipid metabolism. Pearson correlation analysis showed that TNF-α and IL-1β were associated with Prevotellaceae_Ga6A1_group and 3R-hydroxy-docosan-5S-olide, alpha-N-(3-hydroxy-14-methyl-pentadecanoyl)-ornithine, 17-methyl-trans-4,5- methylenenona-decanoic acid, Semiplenamide F. The key differential microbiota genera and differential microbial metabolites may become important targets for the treatment of RA and provide the theoretical basis for exploring the pathogenesis of RA.

The need for high-resolution gut microbiome characterization to design efficient strategies for sustainable aquaculture production

Microbiome-directed dietary interventions such as microbiota-directed fibers (MDFs) have a proven track record in eliciting responses in beneficial gut microbes and are increasingly being promoted as an effective strategy to improve animal production systems. Here we used initial metataxonomic data on fish gut microbiomes as well as a wealth of a priori mammalian microbiome knowledge on α-mannooligosaccharides (MOS) and β-mannan-derived MDFs to study effects of such feed supplements in Atlantic salmon (Salmo salar) and their impact on its gut microbiome composition and functionalities. Our multi-omic analysis revealed that the investigated MDFs (two α-mannans and an acetylated β-galactoglucomannan), at a dose of 0.2% in the diet, had negligible effects on both host gene expression, and gut microbiome structure and function under the studied conditions. While a subsequent trial using a higher (4%) dietary inclusion of β-mannan significantly shifted the gut microbiome composition, there were still no biologically relevant effects on salmon metabolism and physiology. Only a single Burkholderia-Caballeronia-Paraburkholderia (BCP) population demonstrated consistent and significant abundance shifts across both feeding trials, although with no evidence of β-mannan utilization capabilities or changes in gene transcripts for producing metabolites beneficial to the host. In light of these findings, we revisited our omics data to predict and outline previously unreported and potentially beneficial endogenous lactic acid bacteria that should be targeted with future, conceivably more suitable, MDF strategies for salmon.

Diet-microbiome interactions influence lung function in chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) affects 30 million Americans. Previous epidemiologic work has shown that diet can impact pulmonary function in those with and without COPD. Diet is also a major driver of gut microbiome composition and function. Importantly, the gut microbiome has also been associated with lung health (i.e., the gut-lung axis) in both preclinical and clinical studies. Despite this growing body of evidence, many questions remain regarding the gut-lung axis. Specifically, how the microbiome impacts the relationship between diet factors and spirometry or stage of disease in people with COPD is little understood. We hypothesize that there are taxonomic differences in the gut microbiome among the different stages of COPD and that diet microbiome interactions influence pulmonary function. This study aimed to identify how the GI microbiota correlated with the severity of respiratory disease in COPD patients and how the microbiome may mediate the relationship between diet, including fiber and omega-3 fatty acids, and lung function outcomes.

Reinventing gut health: leveraging dietary bioactive compounds for the prevention and treatment of diseases.

The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.

Brief Disruption of Circadian Rhythms Alters Intestinal Barrier Integrity and Modulates DSS-Induced Colitis Severity in Mice.

Physiological processes in organisms exhibit circadian rhythms that optimize fitness and anticipate environmental changes. Luminal signals such as food or metabolites synchronize bowel activity, and disruptions in these rhythms are linked to metabolic disorders and gastrointestinal inflammation. To characterize the intrinsic intestinal rhythms and assess disruptions due to continuous darkness or light exposure, C57BL/6 mice were exposed to standard light-dark conditions or continuous light/darkness for 48h, with evaluations at four timepoints. We assessed intestinal morphology, mucus production, nitric oxide levels and permeability. Under standard light: dark cycles, mice showed changes in intestinal morphology consistent with normal tract physiology. Continuous light exposure caused marked alterations in the small intestine´s epithelium and lamina propria, reduced nitric oxide production in the colon, and predominant neutral mucins. Enhanced permeability was indicated by higher FITC-dextran uptake and increased frequency of IgG-coated bacteria. Additionally, the 48h-disruption influenced DSS-induced colitis with attenuation in L:L group, or exacerbation in D:D group, of clinical signs. These findings highlight the critical role of circadian rhythms in gut histoarchitecture and function, demonstrating that short-term disruptions in light-dark cycles can compromise intestinal barrier integrity and impact inflammatory outcomes.

Full-length 16S rRNA gene amplicon analysis of gut microbiota in pigs fed with different diets in growing and finishing stages

The present study utilized full-length 16S rRNA gene sequencing to investigate the impact of dietary protein content on the composition and function of gut microbiota, and to analyze the gut microbiota of pigs in the growing (30 kg) and finishing (120 kg) stages under different feeding conditions. The results indicated that the gut microbiota was significantly different between pigs fed high- and low-protein diets. Comparing fecal samples from pigs at 30 and 120 kg, pigs at 30 kg showed a significant increase in the relative abundance of Clostridium butyricum, whereas at 120 kg, the abundance of Lactobacillus reuteri and Lactobacillus johnsonii decreased. To access the functional profiles and metabolic pathways based on amplicon sequence variants (ASVs), the microbiome of the 120 kg exhibited significant enrichments in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to metabolism-related category, including Alanine, aspartate and glutamate metabolism, Tyrosine and Thiamin metabolism, and Inositol phosphate metabolism. Meanwhile, analysis using the MetaCyc database showed that the metabolic pathways of the 30 kg group were significantly distinct when compared to the 120 kg of fecal samples. Overall, the findings indicated that the gut microbiota composition and function in the 30 and 120 kg fecal samples were markedly shaped by different dietary protein levels.

Functional Organisation, Predator-prey Interactions, and Gut Content Analysis for Selected Groups of Benthic Macroinvertebrates in High Elevation Ponds in St. Ann Parish, Jamaica

Functional Organisation, Predator-prey Interactions, and Gut Content Analysis for Selected Groups of Benthic Macroinvertebrates in High Elevation Ponds in St. Ann Parish, Jamaica

Functional Organisation, Predator-prey Interactions, and Gut Content Analysis for Selected Groups of Benthic Macroinvertebrates in High Elevation Ponds in St. Ann Parish, Jamaica

Functional Organisation, Predator-prey Interactions, and Gut Content Analysis for Selected Groups of Benthic Macroinvertebrates in High Elevation Ponds in St. Ann Parish, Jamaica