Faecalibacterium prausnitzii is one of the most dominant commensal bacteria in the human gut, and certain anti-inflammatory functions have been attributed to a single microbial anti-inflammatory molecule (MAM). Simultaneously, substantial diversity among F. prausnitzii strains is acknowledged, emphasizing the need for strain-level functional studies aimed at developing innovative probiotics. Here, two distinct F. prausnitzii strains, KBL1026 and KBL1027, were isolated from Korean donors, exhibiting notable differences in the relative abundance of F. prausnitzii. Both strains were identified as the core Faecalibacterium amplicon sequence variant (ASV) within the healthy Korean cohort, and their MAM sequences showed a high similarity of 98.6%. However, when a single strain was introduced to mice with dextran sulfate sodium (DSS)-induced colitis, KBL1027 showed the most significant ameliorative effects, including alleviation of colonic inflammation and restoration of gut microbial dysbiosis. Moreover, the supernatant from KBL1027 elevated the secretion of IL-10 cytokine more than that of KBL1026 in mouse bone marrow-derived macrophage (BMDM) cells, suggesting that the strain-specific, anti-inflammatory efficacy of KBL1027 might involve effector compounds other than MAM. Through analysis of the Faecalibacterium pan-genome and comparative genomics, strain-specific functions related to extracellular polysaccharide biosynthesis were identified in KBL1027, which could contribute to the observed morphological disparities. Collectively, our findings highlight the strain-specific, anti-inflammatory functions of F. prausnitzii, even within the same core ASV, emphasizing the influence of their human origin.

Global warming is a major risk factor for life-threatening heat stroke (HS). Systemic inflammation plays a key role in the pathophysiology of HS, substantially affecting clinical outcomes. Reduced intestinal blood flow during HS causes ischemia-reperfusion injury, compromising the intestinal barrier and triggering systemic inflammation and organ damage. Butyrate, a short-chain fatty acid, plays a multifaceted role in maintaining intestinal health, inhibiting inflammation, and alleviating oxidative stress. Therefore, this study aimed to evaluate butyrate's therapeutic potential against HS and explored the mechanisms underlying its protective effects. Male Wistar rats were divided into 4 groups: control, control + butyrate, HS, and HS + butyrate. Hemodynamic changes, biochemical parameters, coagulation markers, cytokine levels, polymorphonuclear neutrophil infiltration, and survival rates were analyzed. Additionally, ileal samples (from rats) and LS174T cells were used to investigate the effect of butyrate on intestinal function. Heat stress induced cytotoxicity; reduced transepithelial resistance in intestinal goblet cells; and triggered intestinal inflammation, oxidative stress, and apoptosis in HS rats. These rats exhibited systemic inflammation, hypotension, tachycardia, coagulopathy, multiple organ dysfunction, and mortality. Butyrate treatment reduced cytotoxicity and improved transepithelial resistance in LS174T cells. Butyrate also reduced intestinal heat stress, inflammation, oxidative stress, and apoptosis, as well as systemic inflammation in HS rats. Furthermore, butyrate ameliorated hypotension, tachycardia, coagulopathy, and multiple organ dysfunction and increased survival in HS rats. These findings indicate that butyrate is a promising intervention for mitigating heat stress-induced intestinal damage, systemic inflammation, and multiple organ dysfunction.

In the present study, we comprehensively investigated the impacts of the infusion of three short-chain fatty acids (SCFAs), sodium acetate (SA), propionate (SP), and butyrate (SB), to examine their respective roles in the gastrointestinal tract (GIT) health and innate immunity of twenty adult Guanzhong milk goats of 1.5 years of age. Infusion of SCFAs resulted in upregulating the activity of certain antioxidant enzymes in comparison with the control group. The SA group significantly (p < 0.05) increased the activity of the catalase (CAT) in the liver, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in the colon, and maleic dialdehyde (MDA) in the jejunum. SP significantly (p < 0.05) upregulated the activity of the total antioxidant capacity (T-AOC) in the ileum, CAT and MDA in the jejunum, CAT in the colon, and SOD in the liver. SB was significantly (p < 0.05) upregulated the activity of the T-AOC in the ileum, CAT in the jejunum, and T-AOC, CAT, SOD, and GSH-Px in the colon. Infusion of SCFAs resulted in significant (p < 0.05) increases in pro-inflammatory and anti-inflammatory cytokines in the intestine compared to the control group. We found that the SA group significantly (p < 0.05) upregulated the level of interleukin-1 beta (IL-1β) in the ileum and jejunum, as well as the levels of IL-6 and TNF-α in the colon, while the SP group significantly (p < 0.05) increased the level of IL-1β in the jejunum and the level of interleukin-10 (IL-10) in the colon. Furthermore, the SB group significantly (p < 0.05) upregulated levels of IL-1β in the jejunum, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) in the colon, and IL-10 in the cecum. Furthermore, some intestinal tight-junction proteins were significantly increased by SCFA infusion. SA significantly (p < 0.05) increased the claudin level in the ileum and occludin in the colon, while the SP group significantly (p < 0.05) upregulated the level of occludin in the jejunum and the claudin level in the ileum. Moreover, SB significantly (p < 0.05) increased the occludin level in the jejunum, claudin level in the ileum, and zonula occludens-1 (ZO-1) level in the colon and cecum. There are many positive associations among antioxidant, inflammatory cytokine, and tight-junction protein indexes in the liver and intestine. In conclusion, our results suggest that the gastric infusion of SA, SP, and SB might improve goat intestinal health through the positive influence on the antioxidant capacity, pro-inflammatory and anti-inflammatory cytokines, and tight-junction proteins.

To evaluate the efficacy of sodium butyrate (NaB) in ameliorating nonalcoholic fatty liver disease (NAFLD) in animals.

Chinese and English databases (including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wangfang Data, CQVIP, and SinoMed) were searched for literature related to NaB to improve the animal model of NAFLD from the establishment of each database to 2023-02. 2 researchers independently screened the literature and extracted the data. The SYRCLE tool was used to assess risk of bias. The extracted data were analyzed using Revman 5.3 and Stata 17.0.

A total of 1008 relevant references were reviewed, and 12 animal experiments involving 192 animals were included in the analysis: 96 in the NaB group and 96 in the model group. The results showed that animals in the NaB group had significantly lower levels of alanine aminotransferase (standardized mean difference (SMD) = -1.29, 95% confidence interval (CI) (-2.08, -0.49), P = .002], aspartate aminotransferase [SMD = -1.13, 95% CI (-1.75, -0.50), P = .0004], NAFLD activity scores [SMD = -3.19, 95%CI(-4.80, -1.58), P = .0001], triglyceride [SMD = -1.28, 95%CI(-1.66, -0.90), P < .00001] and total cholesterol levels [SMD = -1.39, 95%CI(-2.11, -0.67), P = .0002], interleukin-1β [SMD = -1.40, 95%CI (-1.87, -0.92), P < .00001], interleukin-6 [SMD = -1.38, 95%CI (-1.87, -0.90), P < .00001], tumor necrosis factor-alpha [SMD = -1.69, 95% CI (-2.10, -1.28), P < .00001], and other pro-inflammatory factors, and significantly higher tight junction protein-1 expression [SMD = 1.06, 95% CI (0.43,1.69), P = .0009].

NaB treatment improves liver function in animals with NAFLD, protected the liver tissue, reduced triglyceride and total cholesterol levels, inhibited inflammation, and protected intestinal barrier function.

The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.

Emerging evidence has shown that gut-brain barrier dysfunction occurs at the early stages of ALS. Previous studies demonstrated that sodium butyrate significantly prolonged the life span of ALS mice. Riluzole is the first FDA-approved drug for ALS treatment. We hypothesize that Riluzole and sodium butyrate combined treatment further decreases aggregation of the h-SOD1G93A, restores the gut-brain barrier function, and delays ALS progression. SOD1G93A mice (9-10-week-old) were treated with Riluzole (10 mg/kg, I.P. daily), sodium butyrate (2% in drinking water), or Riluzole and sodium butyrate combination for 6 weeks. The Riluzole/butyrate combination showed a significantly longer rotarod time, increased grip strength, and enhanced intestinal barrier, as compared with Riluzole or sodium butyrate-only treatment. More reduction of h-SOD1G93A aggregation was observed in the colon, spinal cord lumbar, and brain cortex with Riluzole and sodium butyrate combination, compared with Riluzole or sodium butyrate-only treatment. Tight junction proteins (ZO-1 and Claudin-5) significantly increased in the colon, spinal cord lumbar, and brain cortex of mice with Riluzole and sodium butyrate treatment. The Riluzole and sodium butyrate combination reduced serum lipopolysaccharides and h-SOD1G93A aggregation, and inflammatory cytokines more than those in Riluzole or sodium butyrate-only treatment. Overall, Riluzole and sodium butyrate treatment is more effective than either Riluzole or sodium butyrate-only in delaying ALS progress. It provides a potential therapeutic strategy and mechanism by restoring barrier function through the gut-brain axis for ALS.

Many countries have banned the use of antibiotics in livestock feed due to the development of antibiotic-resistant bacteria. Therefore, it is necessary to identify suitable alternatives to antibiotics in order to maintain intestinal health and improve piglet performance after weaning. The objective of this study was to evaluate how the intake of two functional foods-potato protein concentrate (PP) and Saccharomyces boulardii (Sb), either isolated or combined-would affect productive performance and some digestive morphophysiological responses after two weeks post-weaning. We evaluated five diets: SB, with Sb; PPC, with PP; PPC-SB, with a combination of PP and Sb; C-, without antibiotics, Sb, or PP; and C+, with antibiotics. Neither the absence of antibiotics in the diet nor the inclusion of PP and Sb affected performance or digestive organ development during the post-weaning phase. Piglets fed the C+ diet and the PP-Sb combination had higher concentrations of occludin proteins and longer villi in the jejunum compared to those fed C-, PPC, and SB. The use of Sb alone or in combination with PP increased fecal Lactobacillus, while antibiotics reduced coliform bacteria. The PP-Sb combination prevented the atrophy of the jejunal villi and promoted adhesion between enterocytes in the jejunum. Including these functional foods in piglet diets contributed to maintaining intestinal health during the critical post-weaning phase. However, further research is needed to validate and enhance the conclusions of this study.

The harsh conditions of the Qinghai-Tibet Plateau pose significant physiological challenges to local fauna, often resulting in gastrointestinal disorders. However, Tibetan pigs have exhibited remarkable adaptability to the high-altitude stress of the Tibetan Plateau, a phenomenon that remains not fully understood in terms of their gastrointestinal microbiota. This study collected 57 gastrointestinal tract samples from Tibetan pigs (n = 6) and plain black pigs (n = 6) with comparable genetic backgrounds. Samples from the stomach, jejunum, cecum, colon, and rectum, underwent comprehensive metagenomic analysis to elucidate the gut microbiota-related adaptive mechanisms in Tibetan pigs to the extreme high-altitude environment. A predominance of Pseudomonadota was observed within gut microbiome of Tibetan pigs. Significant differences in the microbial composition were also identified across the tested gastrointestinal segments, with 18 genera and 141 species exhibiting differential abundance. Genera such as Bifidobacterium, Megasphaera, Fusobacterium, and Mitsuokella were significantly more abundant in Tibetan pigs than in their lowland counterparts, suggesting specialized adaptations. Network analysis found greater complexity and modularity in the microbiota of Tibetan pigs compared to black pigs, indicating enhanced ecological stability and adaptability. Functional analysis revealed that the Tibetan pig microbiota was particularly enriched with bacterial species involved in metabolic pathways for propionate and butyrate, key short-chain fatty acids that support energy provision under low-oxygen conditions. The enzymatic profiles of Tibetan pigs, characterized by elevated levels of 4-hydroxybutyrate dehydrogenase and glutaconyl-CoA decarboxylase, highlighted a robust fatty acid metabolism and enhanced tricarboxylic acid cycle activity. In contrast, the gut microbiome of plain black pigs showed a reliance on the succinate pathway, with a reduced butyrate metabolism and lower metabolic flexibility. Taken together, these results demonstrate the crucial role of the gastrointestinal microbiota in the adaptation of Tibetan pigs to high-altitude environments by optimizing carbohydrate metabolism and short-chain fatty acid production for efficient energy utilization. This study not only highlights the metabolic benefits conferred by the gut microbiota of Tibetan pigs in extreme environments, but also advances our understanding of the adaptive gastrointestinal mechanisms in plateau-dwelling animals. These insights lay the foundation for exploring metabolic interventions to support health and performance in high-altitude conditions.

Aging is an extremely significant risk associated with neurodegeneration. The most prevalent neurodegenerative disorders (NDs), such as Alzheimer's disease (AD) are distinguished by the prevalence of proteinopathy, aberrant glial cell activation, oxidative stress, neuroinflammation, defective autophagy, cellular senescence, mitochondrial dysfunction, epigenetic changes, neurogenesis suppression, increased blood-brain barrier permeability, and intestinal dysbiosis that is excessive for the patient's age. Substantial body studies have documented a close relationship between gut microbiota and AD, and restoring a healthy gut microbiota may reduce or even ameliorate AD symptoms and progression. Thus, control of the microbiota in the gut has become an innovative model for clinical management of AD, and rising emphasis is focused on finding new techniques for preventing and/or managing the disease. The etiopathogenesis of gut microbiota in driving AD progression and supplementing postbiotics as a preventive and therapeutic treatment for AD is discussed. The review additionally discusses the use of postbiotics in AD prophylaxis and therapy, portraying them as substances that address senescence-triggered dysfunctions and are worthy of translating from bench to biopharmaceutical market in response to "silver consumers" needs. The current review examines and evaluates the impact of postbiotics as whole and specific metabolites, such as short-chain fatty acids (SCFAs), lactate, polyamines, polyphenols, tryptophan metabolites, exopolysaccharides, and bacterial extracellular vesicles, on the aging-associated processes that reinforce AD. Moreover, it provides an overview of the most recent data from both clinical and preclinical research involving the use of postbiotics in AD.

The role of gut microbiota has become a research hotspot in recent years; however, whether the gut microbiota are involved in the alleviation or exacerbation of Deoxynivalenol (DON) toxicity has not been fully studied. Therefore, the objective of this study was to investigate whether the gut microbiota are involved in reducing or aggravating the intestinal damage induced by DON in mice. Mice that received or did not receive antibiotic-induced intestinal flora clearance were orally given DON (5 mg kg/bw/day) for 14 days. At the end of the experiment, serum, intestinal tissue samples and colon contents were collected for further analysis. DON caused development of severe histopathological damage, such as necrosis and inflammation of the jejunum and colon in mice without gut microbiota clearance. The levels of tight junction proteins ZO-1 and occludin were reduced in the jejunum and colon of mice without gut microbiota clearance. In addition, the mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased in mice without gut microbiota clearance. The presence of microbiota exacerbate the intestinal damage induced by DON via changes in gut microbiota abundance and production of gut damaging metabolites.

Ca2+ and Mg2+ are essential nutrients, and deficiency can cause serious health problems. Thus, lack of Ca2+ and Mg2+ can lead to osteoporosis, with incidence rising both in absolute and age-specific terms, while Mg2+ deficiency is associated with type II diabetes. Prevention via vitamin D or estrogen is controversial, and the bioavailability of Ca2+ and Mg2+ from supplements is significantly lower than that from milk products. Problems are likely to increase as populations age and the number of people on vegan diets surges. Developing new therapeutic strategies requires a better understanding of the molecular mechanisms involved in absorption by intestinal epithelia. The vitamin-D dependent, active pathway for the uptake of Ca2+ from the upper small intestine involving TRPV6 is highly efficient but only accounts for about 20% of total uptake. Instead, most Ca2+ uptake is thought to occur via passive paracellular diffusion across the ileum, although sufficiently high luminal concentrations are difficult to achieve.. Interestingly, colon and caecum also have a considerable capacity for the active absorption of Ca2+ and Mg2+, the molecular mechanisms of which are unclear. Intriguingly, stimulating fermentation by prebiotics enhances colonic absorption, which can rise from ~10% to ~30% of the total. Notably, fermentation releases protons, which inhibits channels highly selective for Ca2+ and Mg2+ (TRPV6 and TRPM6/TRPM7). Conversely, the non-selective cation channel TRPV3 is stimulated by both intracellular acidification and by numerous herbal compounds. Spicy, fiber-rich food, as traditionally consumed in many cultures, might enhance the uptake of Ca2+ and Mg2+ via this pathway.

The prevalence of gestational diabetes mellitus (GDM), a condition that is widespread globally, is increasing. The relationship between the gut microbiota and GDM has been a subject of research for nearly two decades, yet there has been no bibliometric analysis of this correlation. This study aimed to use bibliometrics to explore the relationship between the gut microbiota and GDM, highlighting emerging trends and current research hotspots in this field.

A total of 394 papers were included in the analysis. China emerged as the preeminent nation in terms of the number of publications on the subject, with 128 papers (32.49%), whereas the United States had the most significant impact, with 4,874 citations. The University of Queensland emerged as the most prolific institution, contributing 18 publications. Marloes Dekker Nitert was the most active author with 16 publications, and Omry Koren garnered the most citations, totaling 154. The journal Nutrients published the most studies (28 publications, 7.11%), whereas PLoS One was the most commonly co-cited journal, with a total of 805 citations. With respect to keywords, research focuses can be divided into 4 clusters, namely, "the interrelationship between the gut microbiota and pregnancy, childbirth," "the relationship between adverse metabolic outcomes and GDM," "the gut microbiota composition and metabolic mechanisms" and "microbiota and ecological imbalance." Key areas of focus include the interactions between the gut microbiota and individuals with GDM, as well as the formation and inheritance of the gut microbiota. Increasing attention has been given to the impact of probiotic supplementation on metabolism and pregnancy outcomes in GDM patients. Moreover, ongoing research is exploring the potential of the gut microbiota as a biomarker for GDM. These topics represent both current and future directions in this field.

This study provides a comprehensive knowledge map of the gut microbiota and GDM, highlights key research areas, and outlines potential future directions.

Butyrate supplementation has gained considerable attention for its potential benefits in livestock, particularly concerning intestinal health and growth performance. This review synthesizes recent research on the diverse roles of butyrate, across various livestock species. As a short-chain fatty acid, butyrate is known for enhancing intestinal development, improving immune function, and modulating microbial diversity. Studies indicate that butyrate supports gut barrier integrity, reduces inflammation, and optimizes feed efficiency, especially during the critical weaning and post-weaning periods in calves, piglets, and lambs. Supplementation with butyrate in livestock has been shown to increase average daily gain (ADG), improve gut microbiota balance, promote growth, enhance gut health, boost antioxidant capacity, and reduce diarrhea. Additionally, butyrate plays a role in the epigenetic regulation of gene expression through histone acetylation, influencing tissue development and immune modulation. Its anti-inflammatory and antioxidant effects have been demonstrated across various species, positioning butyrate as a potential therapeutic agent in animal nutrition. This review suggests that optimizing butyrate supplementation strategies to meet the specific needs of each species may yield additional benefits, establishing butyrate as an important dietary additive for enhancing growth performance and health in livestock.

Diabetes mellitus represents a significant global health problem. The number of people suffering from this metabolic disease is constantly rising and although the incidence is heterogeneous depending on region, country, economic situation, lifestyle, diet and level of medical care, it is increasing worldwide, especially among youths and children, mainly due to lifestyle and environmental changes. The pathogenesis of the two most common subtypes of diabetes mellitus, type 1 (T1DM) and type 2 (T2DM), is substantially different, so each form is characterized by a different causation, etiology, pathophysiology, presentation, and treatment. Research in recent decades increasingly indicates the potential role of the gut microbiome in the initiation, development, and progression of this disease. Intestinal microbes and their fermentation products have an important impact on host metabolism, immune system, nutrient digestion and absorption, gut barrier integrity and protection against pathogens. This review summarizes the current evidence on the changes in gut microbial populations in both types of diabetes mellitus. Attention is focused on changes in the abundance of specific bacterial groups at different taxonomic levels in humans, and microbiome shift is also assessed in relation to geographic location, age, diet and antidiabetic drug. The causal relationship between gut bacteria and diabetes is still unclear, and future studies applying new methodological approaches to a broader range of microorganisms inhabiting the digestive tract are urgently needed. This would not only provide a better understanding of the role of the gut microbiome in this metabolic disease, but also the use of beneficial bacterial species in the form of probiotics for the treatment of diabetes.

Globally, one of the most prevalent cancers is colorectal cancer (CRC). Chemotherapy and surgery are two common conventional CRC therapies that are frequently ineffective and have serious adverse effects. Thus, there is a need for complementary and different therapeutic approaches. The use of microbial metabolites to trigger epigenetic alterations as a way of preventing CRC is one newly emerging field of inquiry. Small chemicals called microbial metabolites, which are made by microbes and capable of altering host cell behaviour, are created. Recent research has demonstrated that these metabolites can lead to epigenetic modifications such as histone modifications, DNA methylation, and non-coding RNA regulation, which can control gene expression and affect cellular behaviour. This review highlights the current knowledge on the epigenetic modification for cancer treatment, immunomodulatory and anti-carcinogenic attributes of microbial metabolites, gut epigenetic targeting system, and the role of dietary fibre and gut microbiota in cancer treatment. It also focuses on short-chain fatty acids, especially butyrates (which are generated by microbes), and their cancer treatment perspective, challenges, and limitations, as well as state-of-the-art research on microbial metabolites-induced epigenetic changes for CRC inhibition. In conclusion, the present work highlights the potential of microbial metabolites-induced epigenetic modifications as a novel therapeutic strategy for CRC suppression and guides future research directions in this dynamic field.

High energy diets are a risk factor for intestinal barrier damage. Butyrate, a major energy source for intestinal epithelial cells, has been shown to improve barrier dysfunction and modulate the gut microbiota. In this trial, we examined the preventative effect of coated sodium butyrate (CSB) on high-energy and low-protein (HELP)-induced intestinal barrier injury in laying hens, and also worked to determine the underlying mechanisms by an integrative analysis of gut microbiota and the metabolome. A total of 216 healthy 28-week-old Huafeng laying hens were randomly assigned to 3 groups with 6 replicates each: the CON group (normal diet), HELP group (HELP diet) and CH500 group (500 mg/kg CSB added to HELP diet). The duration of the trial encompassed a period of 10 weeks. The results revealed that CSB treatment improved the laying rate and mitigated the detrimental effects on intestinal barrier function and the inflammatory response induced by the HELP diet in laying hens (P < 0.05). Microbial profiling analysis revealed that the CSB treatment reshaped the HELP-perturbed gut microbiota and promoted the growth of beneficial bacteria (P < 0.05). Untargeted metabolomics analysis revealed that CSB reduced the metabolites associated with intestinal inflammation (P < 0.05). In conclusion, CSB did not merely modulate alterations in the gut microbiota composition and microbial metabolites but also yielded increased egg production, while mitigating intestinal barrier dysfunction and inflammatory responses induced by HELP in laying hens.

Butyric acid as a short-chain fatty acid (SCFA) is one of the key microbial metabolites of ruminants. Numerous studies indicate that butyrate is crucial in muscle growth and development, and plays an important molecular regulatory role mainly by inhibiting histone deacetylation. DNA methylation, a major epigenetic modification, is involved in cell differentiation. Butyrate, in addition to its role in acetylation modifications, can alter the DNA methylation status of cells. However, the impact of butyrate on the DNA methylation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. In this study, we developed a differentiation model of SMSCs and employed RNA sequencing (RNA-seq) alongside whole genome bisulfite sequencing (WGBS) to explore the effects of butyrate treatment on DNA methylation status and its relationship with gene expression. Treatment of SMSCs with sodium butyrate (NaB) at 1.0 mM for 2 days significantly inhibited the expression of DNA methyltransferases (DNMT1, DNMT2, DNMT3A) at the mRNA and protein levels while promoting the expression of demethylases (TET1, TET2, TET3) at mRNA levels. WGBS identified 4292 differentially methylated regions (DMRs), comprising 2294 hypermethylated and 1998 hypomethylated regions. These DMRs were significantly enriched in the MAPK, cAMP, and Wnt signaling pathways, all of which are implicated in myogenesis and development. Combining RNA-seq and WGBS data revealed a total of 130 overlapping genes, including MDFIC, CREBBP, DMD, LTBP2 and KLF4. These genes are predominantly involved in regulating the FoxO, MAPK, PI3K-Akt, and Wnt signaling pathways. This study provides new insights into the effects of butyrate-mediated DNA methylation on SMSC development and enhances our understanding of butyrate as an epigenetic modifier beyond its role in acetylation.

The alteration of the microbiota in the mouth and gut could potentially play a role in the pathogenesis of various diseases, and conversely, these diseases may have an influence on the composition of the gut microbiota. Acromegaly disease can potentially affect physiological processes in the mouth and gut. The present study was designed to investigate the relationship between acromegaly and the oral and gut microbiota, as data on this topic are scarce.

This was a multicenter, cross-sectional study. Our study included individuals diagnosed with acromegaly (who were treated and followed up, and also as an another group of patients with newly diagnosed acromegaly) and healthy participants. All three groups were assessed and compared based on age, sex, serum IGF-1, body mass index BMI as well as their stool and oral microbiota We collected demographic information from the patients, collected fecal and oral samples, performed DNA isolation followed by 16 S rRNA sequencing, and then performed bioinformatic analysis. We also analyzed the oral and fecal samples with respect to medical and surgical treatment and disease control status, specific treatments received for acromegaly, presence of comorbidities, hypopituitarism status, presence of intestinal polyps.

One hundred and three patients with acromegaly, 15 newly diagnosed patients with acromegaly without comorbidities and 34 healthy controls were included in the study. The Firmicutes/Bacteroidetes ratio was significantly lower in patients with acromegaly who received treatment (medical and/or surgical) than in healthy controls. In addition, a significant difference was found in the fecal and oral microbiota of patients with acromegaly with disease control compared to healthy controls. Furthermore, a significant difference was found in the fecal and oral microbiota of patients with acromegaly without disease control. Nevertheless, it was not possible to establish a clear relationship between disease control status, the presence of intestinal polyps, the presence of type 2 diabetes and the composition of the oral and gut microbiota in acromegalic patients who had received different forms of treatment.

Patients with acromegaly show distinct gut microbiota profiles, and it is evident that factors beyond the GH/IGF-1 axis play a role in shaping the gut microbiota of individuals with acromegaly.

The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet-microbiota-host interactions depend on the use of genetically tractable models, such as Drosophila melanogaster. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the Drosophila model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction.

Rheumatoid arthritis is a widely prevalent autoimmune bone disease that imposes a significant burden on global healthcare systems due to its increasing incidence. In recent years, attention has focused on the interaction between gut homeostasis and the immune system, particularly in relation to bone health. Dysbiosis, which refers to an imbalance in the composition and function of the gut microbiota, has been shown to drive immune dysregulation through mechanisms such as the release of pro-inflammatory metabolites, increased gut permeability, and impaired regulatory T cell function. These factors collectively contribute to immune system imbalance, promoting the onset and progression of Rheumatoid arthritis. Dysbiosis induces both local and systemic inflammatory responses, activating key pro-inflammatory cytokines such as tumor necrosis factor-alpha, Interleukin-6, and Interleukin-17, which exacerbate joint inflammation and damage. Investigating the complex interactions between gut homeostasis and immune regulation in the context of Rheumatoid arthritis pathogenesis holds promise for identifying new therapeutic targets, revealing novel mechanisms of disease progression, and offering innovative strategies for clinical treatment.

Over recent years, the scientific community has acknowledged the crucial role of certain microbial strains inhabiting the intestinal ecosystem in promoting human health, and participating in various beneficial functions for the host. These microorganisms are now referred to as next-generation probiotics and are currently considered as biotherapeutic products and food or nutraceutical supplements. However, the majority of next-generation probiotic candidates pose nutritional demands and exhibit high sensitivity towards aerobic conditions, leading to numerous technological hurdles in large-scale production. This underscores the need for the development of suitable delivery systems capable of enhancing the viability and functionality of these probiotic strains. Currently, potential candidates for next generation probiotics (NGP) are being sought among gut bacteria linked to health, which include strains from the genera Bacteroids, Faecalibacterium, Akkermansia and Clostridium. In contrast to Lactobacillus spp. and Bifidobacterium spp., NGP, particularly Bacteroids spp. and Clostridium spp., appear to exhibit greater ambiguity regarding their potential to induce infectious diseases. The present review provides a comprehensive overview of NGPs in terms of their health beneficial effects, regulation framework and risk assessment targeting relevant criteria for commercialization in food and pharmaceutical markets.

Accumulating evidence emphasizes the critical reciprocity between gut microbiota and intestinal barrier function in maintaining the gastrointestinal homeostasis. Given the fundamental role caused by intestinal permeability, which has been scrutinized as a measurable potential indicator of perturbed barrier function in clinical researches, it seems not surprising that recent decades have been marked by augmented efforts to determine the interaction between intestinal microbes and permeability of the individual. However, despite the significant progress in characterizing intestinal permeability and the commensal bacteria in the intestine, the mechanisms involved are still far from being thoroughly revealed. In the present review, based on multiomic methods, high-throughput sequencing and molecular biology techniques, the impacts of gut microbiota on intestinal permeability as well as their complex interaction networks are systematically summarized. Furthermore, the diseases related to intestinal permeability and main causes of changes in intestinal permeability are briefly introduced. The purpose of this review is to provide a novel prospection to elucidate the correlation between intestinal microbiota and permeability, and to explore a promising solution for diagnosis and treatment of gastrointestinal related diseases.

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.

Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut microbiota in human physiology. In this study, we re-analyzed 10 fecal metaproteomics datasets of healthy individuals from different continents and countries, with the aim of identifying stable and variable gut microbial functions and defining the contribution of specific bacterial taxa to the main metabolic pathways. The "core" metaproteome included 182 microbial functions and 83 pathways that were identified in all individuals analyzed. Several enzymes involved in glucose and pyruvate metabolism, along with glutamate dehydrogenase, acetate kinase, elongation factors G and Tu and DnaK, were the proteins with the lowest abundance variability in the cohorts under study. On the contrary, proteins involved in chemotaxis, response to stress and cell adhesion were among the most variable functions. Random-effect meta-analysis of correlation trends between taxa, functions and pathways revealed key ecological and molecular associations within the gut microbiota. The contribution of specific bacterial taxa to the main biological processes was also investigated, finding that Faecalibacterium is the most stable genus and the top contributor to anti-inflammatory butyrate production in the healthy gut microbiota. Active production of other mucosal immunomodulators facilitating host tolerance was observed, including Roseburia flagellin and lipopolysaccharide biosynthetic enzymes expressed by members of Bacteroidota. Our study provides a detailed picture of the healthy human gut microbiota, contributing to unveil its functional mechanisms and its relationship with nutrition, immunity, and environmental stressors.

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.

Antibiotic-associated diarrhea (AAD) is a common side effect of long-term and heavy antibiotic therapy. Weizmannia coagulans (W. coagulans) is an ideal probiotic because of its high viability, stability, and numerous health benefits to the host. In this study, the strains were first screened for W. coagulans WC10 (WC10) with a high combined ability based on their biological properties of gastrointestinal tolerance, adhesion, and short-chain fatty acid production ability. The effect of WC10 on mice with AAD was further evaluated. The results showed that WC10 was effective in improving the symptoms of AAD, effectively restoring antibiotic-induced weight loss, and reducing diarrhea status score and fecal water content. In addition, WC10 decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines, alleviated intestinal tissue damage and inflammation, and improved intestinal epithelial barrier function by decreasing serum levels of enterotoxin, DAO, and D-lactic acid, and by increasing the expression of the intestinal mucosal immune factors sIgA and occludin. Importantly, the composition and function of the gut microbiota gradually recovered after WC10 treatment, increasing the number of SCFAs-producing Bifidobacterium and Roseburia. Subsequently, the short-chain fatty acid (SCFA) content was examined and WC10 significantly increased acetate, propionate, and butyrate production. Additionally, metabolomic analysis also showed that WC10 reversed the antibiotic interference with major metabolic pathways. These findings provide a solid scientific basis for the future application of W. coagulans WC10 in the treatment of AAD.

Endometriosis (EM), a chronic condition in endometrial tissue outside the uterus, affects around 10% of reproductive-age women, significantly affecting fertility. Its prevalence remains elusive due to the surgical confirmation needed for diagnosis. Manifesting with a range of symptoms, including dysmenorrhea, dyschezia, dysuria, dyspareunia, fatigue, and gastrointestinal discomfort, EM significantly impairs quality of life due to severe chronic pelvic pain (CPP). Psychological manifestations, notably depression and anxiety, frequently accompany the physical symptoms, with CPP serving as a key mediator. Pain stems from endometrial lesions, involving oxidative stress, neuroinflammation, angiogenesis, and sensitization processes. Microbial dysbiosis appears to be crucial in the inflammatory mechanisms underlying EM and associated CPP, as well as psychological symptoms. In this scenario, dietary interventions and nutritional supplements could help manage EM symptoms by targeting inflammation, oxidative stress, and the microbiome. Our manuscript starts by delving into the complex relationship between EM pain and psychological comorbidities. It subsequently addresses the emerging roles of the microbiome, inflammation, and oxidative stress as common links among these abovementioned conditions. Furthermore, the review explores how dietary and nutritional interventions may influence the composition and function of the microbiome, reduce inflammation and oxidative stress, alleviate pain, and potentially affect EM-associated psychological disorders.

Exposure to passive heat (acclimation) and exercise under hot conditions (acclimatization), known as heat acclimation (HA), are methods that athletes include in their routines to promote faster recovery and enhance physiological adaptations and performance under hot conditions. Despite the potential positive effects of HA on health and physical performance in the heat, these stimuli can negatively affect gut health, impairing its functionality and contributing to gut dysbiosis. Blood redistribution to active muscles and peripheral vascularization exist during exercise and HA stimulus, promoting intestinal ischemia. Gastrointestinal ischemia can impair intestinal permeability and aggravate systemic endotoxemia in athletes during exercise. Systemic endotoxemia elevates the immune system as an inflammatory responses in athletes, impairing their adaptive capacity to exercise and their HA tolerance. Better gut microbiota health could benefit exercise performance and heat tolerance in athletes. This article suggests that: (1) the intestinal modifications induced by heat stress (HS), leading to dysbiosis and altered intestinal permeability in athletes, can decrease health, and (2) a previously acquired microbial dysbiosis and/or leaky gut condition in the athlete can negatively exacerbate the systemic effects of HA. Maintaining or improving the healthy gut microbiota in athletes can positively regulate the intestinal permeability, reduce endotoxemic levels, and control the systemic inflammatory response. In conclusion, strategies based on positive daily habits (nutrition, probiotics, hydration, chronoregulation, etc.) and preventing microbial dysbiosis can minimize the potentially undesired effects of applying HA, favoring thermotolerance and performance enhancement in athletes.

Thirty-two primiparous and 31 multiparous Alpine goats were used to determine influences of diets varying in level and source of forage on performance in early to mid-lactation for 16 wk. Diets consisted of 40%, 50%, 60%, and 70% forage (designated as 40F, 50F, 60F, and 70F, respectively) with 60F and 70F containing coarsely ground grass hay (primarily orchardgrass) and 40F and 50F containing cottonseed hulls, alfalfa pellets, and coarsely ground wheat hay. Diets contained 15.9% to 16.3% crude protein and 37.8%, 42.1%, 53.5%, and 55.4% neutral detergent fiber (NDF) with 10.0%, 15.8%, 50.1%, and 55.5% particle retention on a 19-mm sieve, and 26.1%, 29.6%, 38.3%, and 40.0% physically effective NDF (peNDF) for 40F, 50F, 60F, and 70F, respectively. Dry matter intake (2.71, 2.75, 1.96, and 1.95 kg/d) and milk yield (2.82, 2.71, 2.23, and 2.10 kg/d for 40F, 50F, 60F, and 70F, respectively) were lower (P < 0.05) for the two diets highest in forage. Digestion of organic matter was similar among diets (P > 0.05), but digestibility of NDF was greater (P < 0.05) for 60F and 70F (57.5%, 58.4%, 68.9%, and 72.2% for 40F, 50F, 60F, and 70F, respectively). Diet affected (P < 0.05) milk fat (3.16%, 3.37%, 2.93%, and 2.97%) and protein concentrations (2.62%, 2.69%, 2.58%, and 2.52% for 40F, 50F, 60F, and 70F, respectively). Milk energy yield was greater (P < 0.05) for the two diets lowest in forage (7.51, 7.45, 5.68, and 5.34 MJ/d), although yield relative to dry matter intake was not affected (P > 0.05) by diet and was lower (P < 0.05) for primiparous vs. multiparous goats (2.71 and 3.09 MJ/kg). Ruminal pH and acetate proportion were greater for 60F and 70F than for the other diets and the proportion of butyrate was lower for the two diets highest in fiber. The mean lengths of time spent ruminating, eating, standing, and lying were not affected (P > 0.05) by diet or parity, but many interactions involving diet, period, hour, and parity were significant (P < 0.05). In conclusion, lactational performance of Alpine goats in early to mid-lactation will be constrained with diets high in forage of moderate quality, peNDF content, and large particle size, which appeared related to limited feed intake.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Although dysbiosis is implicated in its pathogenesis, deep sequencing and oral microbiota study in Chinese IBD patients is absent.

To explore the role of oral / intestinal microbiota in patients with IBD and the potential associations therein.

Clinical data, fecal and saliva samples were harvested from 80 patients with IBD (Crohn's disease, CD, n = 69; Ulcerative colitis, UC, n = 11) and 24 normal controls. Microbiomics (16S rRNA sequencing and 16S rRNA full-length sequencing) were used to detect and analyze the difference between IBD patients and normal control.

Compared with normal controls, a higher abundance of the intestinal Shigella spp. (Shigella flexneri and Shigella sonnei, which were positively relate to the severity of IBD), lower abundance of intestinal probiotics (Prevotella, Faecalibacterium and Roseburia), and higher abundance of oral Neisseria were present in IBD patients with microbiome. The higher inflammation-related markers, impaired hepatic and renal function, and dyslipidaemia were present in patients with IBD. A higher intake of red meat and increased abundance of Clostridium in the gut were found in CD patients, while the elevated abundance of Ruminococcus in the gut was showed in UC ones. The bacterial composition of saliva and fecal samples was completely different, yet there was some correlation in the distribution of dominant probiotics.

Enteric dysbacteriosis and the infections of pathogenic bacteria (Shigella) may associate with the occurrence or development of IBD.

Higher diet quality has been associated with lower risk of developing inflammatory bowel disease, but associations between diet and gastrointestinal (GI) inflammation in healthy adults prior to disease onset are understudied.

The purpose of this project was to examine associations between reported dietary intake and markers of GI inflammation in a healthy adult human cohort.

In a cross-sectional observational trial of 358 healthy adults, participants completed ≤3 unannounced 24-h dietary recalls using the Automated Self-Administered Dietary Assessment Tool and a Block 2014 Food Frequency Questionnaire to assess recent and habitual intake, respectively. Those who provided a stool sample were included in this analysis. Inflammation markers from stool, including calprotectin, neopterin, and myeloperoxidase, were measured by ELISA along with LPS-binding protein from plasma.

Recent and habitual fiber intake was negatively correlated with fecal calprotectin concentrations (n = 295, P = 0.011, 0.009). Habitual soluble fiber intake was also negatively correlated with calprotectin (P = 0.01). Recent and habitual legume and vegetable intake was negatively correlated with calprotectin (P = 0.013, 0.026, 0.01, 0.009). We observed an inverse correlation between recent Healthy Eating Index (HEI) scores and calprotectin concentrations (n = 295, P = 0.026). Dietary Inflammatory Index scores were calculated and positively correlated with neopterin for recent intake (n = 289, P = 0.015). When participants with clinically elevated calprotectin were excluded, recent and habitual fiber, legume, vegetable, and fruit intake were negatively correlated with calprotectin (n = 253, P = 0.00001, 0.0002, 0.045, 0.001, 0.009, 0.001, 0.004, 0.014). Recent total HEI score was inversely correlated with subclinical calprotectin (P = 0.003).

Higher diet quality may be protective against GI inflammation even in healthy adults. This trial was registered at clinicaltrials.gov as NCT02367287.

This study aims to explore the potential interconnections among gut microbiota, COVID-19 infection, depression and anxiety disorder. Additionally, it tries to assess potential therapeutic interventions that may improve the dysbiosis of gut microbiota.

To achieve these objectives, we reviewed existing literature, encompassing studies and critical reviews that intersect the domains of gut microbiota, COVID-19, depression and anxiety disorders.

The findings highlight a notable correlation between the dysbiosis of gut microbiota and psychiatric symptoms in the context of COVID-19. Specifically, there is a marked reduction in the populations of bacteria that generate anti-inflammatory short-chain fatty acids (SCFAs), alongside a rise in the prevalence of gut bacterial clusters linked to inflammatory processes. Furthermore, several potential treatment strategies were summarised for improving the dysbiosis.

Gut microbiota plays a significant role in psychiatric symptoms during COVID-19, which has significant implications for the study and prevention of psychiatric symptoms in major epidemic diseases.

Alcohol use disorder (AUD) represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality. The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders. Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD, with alcohol consumption directly impacting its composition and function. This review article aims to explore the intricate relationship between the gut microbiome and AUD, focusing on the implications for mental health outcomes and potential therapeutic strategies. We discuss the bidirectional communication between the gut microbiome and the brain, highlighting the role of microbiota-derived metabolites in neuroinflammation, neurotransmission, and mood regulation. Furthermore, we examine the influence of AUD-related factors, such as alcohol-induced gut dysbiosis and increased intestinal permeability, on mental health outcomes. Finally, we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD, including prebiotics, probiotics, and fecal microbiota transplantation. Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.

In recent years, the increase in high-calorie diets and sedentary lifestyles has made obesity a global public health problem. An unbalanced diet promotes the production of proinflammatory cytokines and causes redox imbalance in the body. Phenolics have potent antioxidant activity and cytoprotective ability. They can scavenge free radicals and reactive oxygen species, and enhance the activity of antioxidant enzymes, thus combating the body's oxidative stress. They can also improve the body's inflammatory response, enhance the enzyme activity of lipid metabolism, and reduce the contents of cholesterol and triglyceride. Most phenolics are biotransformed and absorbed into the blood after the action by gut microbiota; these metabolites then undergo phase I and II metabolism and regulate oxidative stress by scavenging free radicals and increasing expression of antioxidant enzymes. Phenolics induce the expression of genes encoding antioxidant enzymes and phase II detoxification enzymes by stimulating Nrf2 to enter the nucleus and bind to the antioxidant response element after uncoupling from Keap1, thereby promoting the production of antioxidant enzymes and phase II detoxification enzymes. The absorption rate of phenolics in the small intestine is extremely low. Most phenolics reach the colon, where they interact with the microbiota and undergo a series of metabolism. Their metabolites will reach the liver via the portal vein and undergo conjugation reactions. Subsequently, the metabolites reach the whole body to exert biological activity by traveling with the systemic circulation. Phenolics can promote the growth of probiotics, reduce the ratio of Firmicutes/Bacteroidetes (F/B), and improve intestinal microecological imbalance. This paper reviews the nutritional value, bioactivity, and antioxidant mechanism of phenolics in the body, aiming to provide a scientific basis for the development and utilization of natural antioxidants and provide a reference for elucidating the mechanism of action of phenolics for regulating oxidative stress in the body. © 2023 Society of Chemical Industry.

A reduced capacity for butyrate production by the early infant gut microbiota is associated with negative health effects, such as inflammation and the development of allergies. Here, we develop new hypotheses on the effect of the prebiotic galacto-oligosaccharides (GOS) or 2'-fucosyllactose (2'-FL) on butyrate production by the infant gut microbiota using a multiscale, spatiotemporal mathematical model of the infant gut. The model simulates a community of cross-feeding gut bacteria in metabolic detail. It represents the community as a grid of bacterial populations that exchange metabolites, using 20 different subspecies-specific metabolic networks taken from the AGORA database. The simulations predict that both GOS and 2'-FL promote the growth of Bifidobacterium, whereas butyrate producing bacteria are only consistently abundant in the presence of propane-1,2-diol, a product of 2'-FL metabolism. In absence of prebiotics or in presence of only GOS, however, Bacteroides vulgatus and Cutibacterium acnes outcompete butyrate producers by consuming intermediate metabolites.

Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT).

We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design.

Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with Faecalibacterium (phylum Firmicutes) and positively correlated with Bacteroides sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with Lactobacillus sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of Lactobacillus sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition.

Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior.

https://clinicaltrials.gov/, CRD42020158734.

People living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls.

PLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid.

We identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications. Video Abstract.