Modulation of human gut microbiota by linear and branched fructooligosaccharides in an in vitro colon model (TIM-2).

AIMS: This study aimed to compare the effects of linear and branched fructooligosaccharides (FOS) extracted from chicory and grass (Lolium perenne), respectively on human microbiota composition, diversity, and metabolism. METHODS AND RESULTS: To test the effects of linear and branched FOS on human microbiota we used the artificial in vitro human colon model (TIM-2). Microbiota composition and diversity were assessed by V3-V4 16S rRNA metagenomic sequencing, followed by differential taxa abundance and alpha/beta diversity analyses. SCFA/BCFA production was evaluated by gas chromatography-mass spectrometry. As a result, branched FOS had the most beneficial effects on microbial diversity and metabolite production. Also, branched FOS significantly increased the abundance of commensal bacteria associated with maintaining healthy gut functions and controlling inflammation, such as Butyricicoccus, Erysipelotrichaceae, Phascolarctobacterium, and Sutterella. Linear FOS also significantly increased the abundance of some other commensal gut bacteria (Anaerobutyricum, Lachnospiraceae, Faecalibacterium), but there were no differences in diversity metrics compared to the control. CONCLUSIONS: The study revealed that branched FOS had the most beneficial effects compared to the linear FOS in vitro, concerning microbiota modulation, and metabolite production, making this a good candidate for further studies in food biotechnology.

Cross-domain microbiomes: the interaction of gut, lung and environmental microbiota in asthma pathogenesis.

Recent experimental and epidemiological studies underscore the vital interaction between the intestinal microbiota and the lungs, an interplay known as the "gut-lung axis". The significance of this axis has been further illuminated following the identification of intestinal microbial metabolites, such as short-chain fatty acids (SCFA), as key mediators in setting the tone of the immune system. Through the gut-lung axis, the gut microbiota and its metabolites, or allergens, are directly or indirectly involved in the immunomodulation of pulmonary diseases, thereby increasing susceptibility to allergic airway diseases such as asthma. Asthma is a complex outcome of the interplay between environmental factors and genetic predispositions. The concept of the gut-lung axis may offer new targets for the prevention and treatment of asthma. This review outlines the relationships between asthma and the respiratory microbiome, gut microbiome, and environmental microbiome. It also discusses the current advancements and applications of microbiomics, offering novel perspectives and strategies for the clinical management of chronic respiratory diseases like asthma.

Is the Mediterranean Low Fodmap Diet Effective in Managing Irritable Bowel Syndrome Symptoms and Gut Microbiota? An Innovative Research Protocol.

INTRODUCTION: Irritable bowel syndrome (IBS) symptoms can be effectively managed with the low FODMAP diet. However, its efficacy in reducing inflammation is not yet proven. On the contrary, the Mediterranean diet has anti-inflammatory properties with proven efficacy in treating chronic low-grade inflammation-related diseases. AIM: To publicly share our protocol evaluating the efficacy of the Mediterranean low-FODMAP (MED-LFD) versus NICE recommendations (British National Institute for Health and Care Excellence) diet in managing IBS symptoms and quality of life. MATERIALS AND METHODS: Participants meeting the Rome IV criteria will be randomly assigned to MED-LFD or NICE recommendations and they will be followed for six months. Efficacy, symptom relief, quality of life and mental health will be assessed using validated questionnaires. In addition, fecal samples will be analyzed to assess gut microbiota, and to measure branched and short-chain fatty acids, and volatile organic compounds (metabolic byproducts from bacteria). Expected results and discussion: By publicly sharing this clinical study protocol, we aim to improve research quality in the field of IBS management by allowing for peer review feedback, preventing data manipulation, reducing redundant research efforts, mitigating publication bias, and empowering patient decision-making. We expect that this protocol will show that MED-LFD can effectively alleviate IBS symptoms and it will provide pathophysiology insights on its efficacy. The new dietary pattern that combines the LFD and the MED approaches allows for the observation of the synergistic action of both diets, with the MED's anti-inflammatory and prebiotic properties enhancing the effects of the LFD while minimizing its limitations. Identifier in Clinical Trials: NCT03997708.

Prebiotic fibre mixtures counteract the manifestation of gut microbial dysbiosis induced by the chemotherapeutic 5-Fluorouracil (5-FU) in a validated in vitro model of the colon.

BACKGROUND: 5-Fluorouracil (5-FU) is used as an antineoplastic agent in distinct cancer types. Increasing evidence suggests that the gut microbiota might modulate 5-FU efficacy and toxicity, potentially affecting the patient's prognosis. The current experimental study investigated 5-FU-induced microbiota alterations, as well as the potential of prebiotic fibre mixtures (M1-M4) to counteract these shifts. METHODS: A pooled microbial consortium was derived from ten healthy donors, inoculated in an in vitro model of the colon, and treated with 5-FU, with or without prebiotic fibre mixtures for 72 h. Four different prebiotic fibre mixtures were tested: M1 containing short-chain galacto-oligosaccharides (sc GOS), long-chain fructo-oligosaccharides (lcFOS), and low viscosity pectin (lvPect), M2 consisting of arabinoxylan, beta-glucan, pectin, and resistant starch, M3 which was a mixture of scGOS and lcFOS, and M4 containing arabinoxylan, beta-glucan, pectin, resistant starch, and inulin. RESULTS: We identified 5-FU-induced changes in gut microbiota composition, but not in microbial diversity. Administration of prebiotic fibre mixtures during 5-FU influenced gut microbiota composition and taxa abundance. Amongst others, prebiotic fibre mixtures successfully stimulated potentially beneficial bacteria (Bifidobacterium, Lactobacillus, Anaerostipes, Weissella, Olsenella, Senegalimassilia) and suppressed the growth of potentially pathogenic bacteria (Klebsiella, Enterobacter) in the presence of 5-FU. The short-chain fatty acid (SCFA) acetate increased slightly during 5-FU, but even more during 5-FU with prebiotic fibre mixtures, while propionate was lower due to 5-FU with or without prebiotic fibre mixtures, compared to control. The SCFA butyrate and valerate did not show differences among all conditions. The branched-chain fatty acids (BCFA) iso-butyrate and iso-valerate were higher in 5-FU, but lower in 5-FU + prebiotics, compared to control. CONCLUSIONS: These data suggest that prebiotic fibre mixtures represent a promising strategy to modulate 5-FU-induced microbial dysbiosis towards a more favourable microbiota, thereby possibly improving 5-FU efficacy and reducing toxicity, which should be evaluated further in clinical studies.

Intermittent fasting and high-intensity interval training do not alter gut microbiota composition in adult women with obesity.

Obesity is advancing at an accelerated pace and yet its treatment is still an emerging field. Although studies have demonstrated the role of the microbiota in the pathogenesis of obesity, this is the first study to show the effects of intermittent fasting (IF), combined or not with exercise (HIIT), on the gut microbiota composition in women with obesity. Our hypothesis is that IF combined with HIIT can promote the remodeling of the composition and function of the gut microbiota. Thirty-six women with obesity participated in the study, aged between 18 and 40 years, randomly divided into 3 groups: 1) IF associated with HIIT group (IF+EX, n = 15); 2) HIIT group (EX, n = 11); and 3) IF group (IF, n = 10). Interventions took place over 8 weeks and all assessments were performed pre- and post-intervention. The HIIT circuit was performed 3x/week, for 25 minutes/session. The IF protocol was a 5:2 (2x/week). Multiplex analysis of inflammatory cytokines, sequencing of the 16S rRNA gene, and gas chromatography to measure fecal concentrations of short-chain fatty acids (SCFAs) were performed. This study was registered on ClinicalTrials.gov (NCT05237154). Exercise increased fecal acetate concentrations (P = 0.04), but no changes were observed in the composition and functional profile of the microbiota. The interventions did not change the composition of the microbiota, but exercise may play a modulatory role in the production of acetate. This investigation provides clinical insights into the use of IF and HIIT for women with obesity.

Potential Prebiotic Effect of Inulin-Enriched Pasta after In Vitro Gastrointestinal Digestion and Simulated Gut Fermentation.

In the current study, the prebiotic potential of an innovative functional pasta enriched with 12% (w/w) inulin was investigated. To this aim, pasta was subjected to in vitro gastrointestinal digestion followed by simulated gut fermentation compared to the control pasta (CTRL) not containing inulin. The incorporation of inulin positively (p < 0.05) affected some organoleptic traits and the cooking quality of the final product, giving an overall score significantly higher than CTRL. The resultant essential amino acid content was similar in both pasta samples while the total protein content was lower in inulin-enriched pasta for the polymer substitution to durum wheat flour. The prebiotic potential of chicory inulin was preliminarily tested in in vitro experiments using seven probiotic strains and among them Lacticaseibacillus paracasei IMPC2.1 was selected for the simulated gut fermentation studies. The positive prebiotic activity score registered with the probiotic strain suggested the suitability of the inulin-enriched pasta with respect to acting as a prebiotic source favoring the growth of the probiotic strain and short chain fatty acid (SCFA) production. The present study contributes to broadening knowledge on the prebiotic efficacy of inulin when incorporated into a complex food matrix.

Therapeutic potential of probiotics in gut microbial homeostasis and Rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint damage. Existing treatment options primarily focus on managing symptoms and slowing disease progression, often with side effects and limitations. The gut microbiome, a vast community of microorganisms present in the gastrointestinal tract, plays a crucial role in health and disease. Recent research suggests a bidirectional relationship between the gut microbiome and RA, highlighting its potential as a therapeutic option. This review focuses on the interaction between the gut microbiome and RA development, by discussing how dysbiosis, an imbalance in gut bacteria, can contribute to RA through multiple mechanisms such as molecular mimicry, leaky gut, and metabolic dysregulation. Probiotics, live microorganisms with health benefits, are emerging as promising tools for managing RA. They can prevent the negative effects of dysbiosis by displacing harmful bacteria, producing anti-inflammatory metabolites like short-chain fatty acids (SCFA), Directly influencing immune cells, and modifying host metabolism. animal and clinical studies demonstrate the potential of probiotics in improving RA symptoms and disease outcomes. However, further research is needed to optimize probiotic strains, dosages, and treatment protocols for personalized and effective management of RA. This review summarizes the current understanding of the gut microbiome and its role in RA and discusses future research directions. In addition to the established role of gut dysbiosis in RA, emerging strategies like fecal microbiota transplantation, prebiotics, and postbiotics offer exciting possibilities. However, individual variations in gut composition necessitate personalized treatment plans. Long-term effects and clear regulations need to be established. Future research focusing on metagenomic analysis, combination therapies, and mechanistic understanding will unlock the full potential of gut microbiome modulation for effective RA management.

Serum-Derived Bovine Immunoglobulin Promotes Barrier Integrity and Lowers Inflammation for 24 Human Adults Ex Vivo.

Serum-derived bovine immunoglobulin (SBI) prevents translocation and inflammation via direct binding of microbial components. Recently, SBI also displayed potential benefits through gut microbiome modulation. To confirm and expand upon these preliminary findings, SBI digestion and colonic fermentation were investigated using the clinically predictive ex vivo SIFR® technology (for 24 human adults) that was, for the first time, combined with host cells (epithelial/immune (Caco-2/THP-1) cells). SBI (human equivalent dose (HED) = 2 and 5 g/day) and the reference prebiotic inulin (IN; HED = 2 g/day) significantly promoted gut barrier integrity and did so more profoundly than a dietary protein (DP), especially upon LPS-induced inflammation. SBI also specifically lowered inflammatory markers (TNF-α and CXCL10). SBI and IN both enhanced SCFA (acetate/propionate/butyrate) via specific gut microbes, while SBI specifically stimulated valerate/bCFA and indole-3-propionic acid (health-promoting tryptophan metabolite). Finally, owing to the high-powered cohort (n = 24), treatment effects could be stratified based on initial microbiota composition: IN exclusively stimulated (acetate/non-gas producing) Bifidobacteriaceae for subjects classifying as Bacteroides/Firmicutes-enterotype donors, coinciding with high acetate/low gas production and thus likely better tolerability of IN. Altogether, this study strongly suggests gut microbiome modulation as a mechanism by which SBI promotes health. Moreover, the SIFR® technology was shown to be a powerful tool to stratify treatment responses and support future personalized nutrition approaches.

Effects of Bifidobacterium animalis subsp. lactis BB-12 and yogurt on mice during oral antibiotic administration.

Probiotics have the potential to prevent disruptions to normal gastrointestinal function caused by oral antibiotic use. In this study, we examined the capacity of Bifidobacterium animalis subspecies lactis BB-12 (BB-12) and yogurt, separately and combined, to mitigate the effects of the antibiotic amoxicillin-clavulanate (AMC) on the gut microbiota and metabolomes of C57BL/6 J mice. Male and female mice were administered either BB-12, yogurt, BB-12 in yogurt, or saline for 10 days concurrent with the inclusion of AMC in the drinking water. Male mice exposed to AMC exhibited significant reductions (p<0.05) in body weight over the course of the study compared to sham (no AMC) controls whereas no such effects were observed for female mice. AMC administration resulted in rapid alterations to the intestinal microbiota in both sexes irrespective of BB-12 or yogurt treatment, including significant (p<0.05) losses in bacterial cell numbers and changes in microbial alpha-diversity and beta-diversity in the feces and cecal contents. The effects of AMC on the gut microbiota were observed within one day of administration and the bacterial contents continued to change over time, showing a succession marked by rapid reductions in Muribaculaceae and Lachnospiraceae and temporal increases in proportions of Acholeplasmataceae (day 1) and Streptococcaceae and Leuconostocaceae (day 5). By day 10 of AMC intake, high proportions of Gammaproteobacteria assigned as Erwiniaceae or Enterobacteriaceae (average of 63 %), were contained in the stools and were similarly enriched in the cecum. The cecal contents of mice given AMC harbored significantly reduced concentrations of (branched) short-chain fatty acids (SCFA), aspartate, and other compounds, whereas numerous metabolites, including formate, lactate, and several amino acids and amino acid derivatives were significantly enriched. Despite the extensive impact of AMC, starting at day 7 of the study, the body weights of male mice given yogurt or BB-12 (in saline) with AMC were similar to the healthy controls. BB-12 (in saline) and yogurt intake was associated with increased Streptococcaceae and both yogurt and BB-12 resulted in lower proportions of Erwiniaceae in the fecal and cecal contents. The cecal contents of mice fed BB-12 in yogurt contained levels of formate, glycine, and glutamine that were equivalent to the sham controls. These findings highlight the potential of BB-12 and yogurt to mitigate antibiotic-induced gut dysbiosis.

Simulated Swine Digestion and Gut Microbiota Fermentation of Hydrolyzed Copra Meal.

This study aimed to compare the effects of hydrolyzed copra meal (HCM) inclusion at 1% on its in vitro digestibility and the microbiota and cecum fermentation using the gut microbiota of weaned swine, targeting microbial community and short-chain fatty acids (SCF). For this reason, three treatments were considered: control (no copra meal), 1% non-hydrolyzed copra meal (CM), and 1% HCM. Non-defatted copra meal was hydrolyzed and analyzed (reducing sugars and total carbohydrates) in our laboratory. For digestion, microbiota identification, and fermentation assays, fresh fecal samples from two weaned pigs (1 month old) were used. Three replicates of each treatment were employed. HCM was more digestible, with approximately 0.68 g of hydrolysate recovered after simulated digestion compared to 0.82 g of hydrolysate recovered from CM. This was shown by Scanning Electron Microscope (SEM) images. Also, the three swine shared the majority of microbial species identified at the phylum and family levels. There were no differences (p > 0.05) between treatments in the microbial community and SCFA during fermentation. However, higher Chao-1 and Shannon indexes were observed in CM and HCM treatments. HCM was also found to be capable of preserving Actinobacterota and Proteobacteria at the phylum level, while at the family level, both treatments may help Lactobacillaceae, Peptostreptococcaceae, Lachnospiraceae, and Ruminococcaceae survive in the long term. Also, there was a potential trend of increasing acetic acid and butyric acid in the CM and HCM treatments. While HCM shows promise in potentially modulating the gut microbiota of weaned swine, additional research is required to investigate the effects of higher doses of HCM on swine performance parameters.

Mechanistic Review on the Role of Gut Microbiota in the Pathology of Cardiovascular Diseases.

Cardiovascular diseases (CVDs), which stand as the primary contributors to illness and death on a global scale, include vital risk factors like hyperlipidemia, hypertension, diabetes, and smoking, to name a few. However, conventional cardiovascular risk factors offer only partial insight into the complexity of CVDs. Lately, a growing body of research has illuminated that the gut microbiome and its by-products are also of paramount importance in the initiation and progression of CVDs. The gastrointestinal tract houses trillions of microorganisms, commonly known as gut microbiota, that metabolize nutrients, yielding substances like trimethylamine- N-oxide (TMAO), bile acids (BAs), short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and so on. Strategies aimed at addressing these microbes and their correlated biological pathways have shown promise in the management and diagnosis of CVDs. This review offers a comprehensive examination of how the gut microbiota contributes to the pathogenesis of CVDs, particularly atherosclerosis, hypertension, heart failure (HF), and atrial fibrillation (AF), explores potential underlying mechanisms, and highlights emerging therapeutic prospects in this dynamic domain.

Probiotics and microbial metabolites maintain barrier and neuromuscular functions and clean protein aggregation to delay disease progression in TDP43 mutation mice.

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. The ALS mice expressing human mutant of transactive response DNA binding protein of 43 kDa (hmTDP43) showed intestinal dysfunction before neuromuscular symptoms. We hypothesize that restoring the intestinal and microbial homeostasis with a bacterial metabolite or probiotics delays the ALS disease onset. We investigate the pathophysiological changes in the intestine and neurons, intestinal and blood-brain barriers, and inflammation during the ALS progression. We then cultured enteric glial cells (EGCs) isolated from TDP43 mice for mechanistic studies. TDP43 mice had significantly decreased intestinal mobility, increased permeability, and weakened muscle, compared with the age-matched wild-type mice. We observed increased hmTDP43 and Glial fibrillary acidic protein (GFAP), and decreased expression of α-smooth muscle actin (α-SMA), tight junction proteins (ZO-1 and Claudin-5) in the colon, spinal cord, and brain in TDP43 mice. TDP43 mice had reduced Butyryl-coenzyme A CoA transferase, decreased butyrate-producing bacteria Butyrivibrio fibrisolvens, and increased Bacteroides fragilis, compared to the WT mice. Serum inflammation cytokines (IL-6, IL-17, and IFN-γ) and LPS were elevated in TDP43 mice. EGCs from TDP43 mice showed aggregation of hmTDP43 associated with increased GFAP and ionized calcium-binding adaptor molecule (IBA1, a microglia marker). TDP43 mice treated with butyrate or probiotic VSL#3 had significantly increased rotarod time, increased intestinal mobility and decreased permeability, compared to the untreated group. Butyrate or probiotics treatment decreased the expression of GFAP, TDP43, and increased α-SMA, ZO-1, and Claudin-5 in the colon, spinal cord, and brain. Also, butyrate or probiotics treatment enhanced the Butyryl-coenzyme A CoA transferase, Butyrivibrio fibrisolvens, and reduced inflammatory cytokines in TDP43 mice. The TDP43 EGCs treated with butyrate or probiotics showed reduced GFAP, IBA1, and TDP43 aggregation. Restoring the intestinal and microbial homeostasis by beneficial bacteria and metabolites provide a potential therapeutic strategy to treat ALS.

Molecular mechanisms and therapeutic possibilities of short-chain fatty acids in posttraumatic stress disorder patients: a mini-review.

This mini-review explores the role of short-chain fatty acids (SCFAs) in posttraumatic stress disorder (PTSD). Highlighting the microbiota-gut-brain axis, this study investigated the bidirectional communication between the gut microbiome and mental health. SCFAs, byproducts of gut microbial fermentation, have been examined for their potential impact on PTSD, with a focus on molecular mechanisms and therapeutic interventions. This review discusses changes in SCFA levels and bacterial profiles in individuals with PTSD, emphasizing the need for further research. Promising outcomes from clinical trials using probiotics and fermented formulations suggest potential avenues for PTSD management. Future directions involve establishing comprehensive human cohorts, integrating multiomics data, and employing advanced computational methods, with the goal of deepening our understanding of the role of SCFAs in PTSD and exploring microbiota-targeted interventions.

Periodontal Inflammation and Dysbiosis Relate to Microbial Changes in the Gut.

Periodontal disease (PerioD) is a chronic inflammatory disease of dysbiotic etiology. Animal models and few human data showed a relationship between oral bacteria and gut dysbiosis. However, the effect of periodontal inflammation and subgingival dysbiosis on the gut is unknown. We hypothesized that periodontal inflammation and its associated subgingival dysbiosis contribute to gut dysbiosis even in subjects free of known gut disorders. We evaluated and compared elderly subjects with Low and High periodontal inflammation (assessed by Periodontal Inflamed Surface Area (PISA)) for stool and subgingival derived bacteria (assayed by 16S rRNA sequencing). The associations between PISA/subgingival dysbiosis and gut dysbiosis and bacteria known to produce short-chain fatty acid (SCFA) were assessed. LEfSe analysis showed that, in Low PISA, species belonging to Lactobacillus, Roseburia, and Ruminococcus taxa and Lactobacillus zeae were enriched, while species belonging to Coprococcus, Clostridiales, and Atopobium were enriched in High PISA. Regression analyses showed that PISA associated with indicators of dysbiosis in the gut mainly reduced abundance of SCFA producing bacteria (Radj = -0.38, p = 0.03). Subgingival bacterial dysbiosis also associated with reduced levels of gut SCFA producing bacteria (Radj = -0.58, p = 0.002). These results suggest that periodontal inflammation and subgingival microbiota contribute to gut bacterial changes.

Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice.

BACKGROUND: Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. The development of novel therapeutic and preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between the gut microbiome and microbial metabolites with drinking behavior, but druggable targets and their underlying mechanism of action are understudied. RESULTS: Here, using a drink-in-the-dark mouse model, we identified a microbiome metabolite-based novel treatment (sodium valerate) that can reduce excessive alcohol drinking. Sodium valerate is a sodium salt of valeric acid short-chain fatty acid with a similar structure as γ-aminobutyric acid (GABA). Ten days of oral sodium valerate supplementation attenuates excessive alcohol drinking by 40%, reduces blood ethanol concentration by 53%, and improves anxiety-like or approach-avoidance behavior in male mice, without affecting overall food and water intake. Mechanistically, sodium valerate supplementation increases GABA levels across stool, blood, and amygdala. It also significantly increases H4 acetylation in the amygdala of mice. Transcriptomics analysis of the amygdala revealed that sodium valerate supplementation led to changes in gene expression associated with functional pathways including potassium voltage-gated channels, inflammation, glutamate degradation, L-DOPA degradation, and psychological behaviors. 16S microbiome profiling showed that sodium valerate supplementation shifts the gut microbiome composition and decreases microbiome-derived neuroactive compounds through GABA degradation in the gut microbiome. CONCLUSION: Our findings suggest that sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms. Video Abstract.

The gut-immune axis during hypertension and cardiovascular diseases.

The gut-immune axis is a relatively novel phenomenon that provides mechanistic links between the gut microbiome and the immune system. A growing body of evidence supports it is key in how the gut microbiome contributes to several diseases, including hypertension and cardiovascular diseases (CVDs). Evidence over the past decade supports a causal link of the gut microbiome in hypertension and its complications, including myocardial infarction, atherosclerosis, heart failure, and stroke. Perturbations in gut homeostasis such as dysbiosis (i.e., alterations in gut microbial composition) may trigger immune responses that lead to chronic low-grade inflammation and, ultimately, the development and progression of these conditions. This is unsurprising, as the gut harbors one of the largest numbers of immune cells in the body, yet is a phenomenon not entirely understood in the context of cardiometabolic disorders. In this review, we discuss the role of the gut microbiome, the immune system, and inflammation in the context of hypertension and CVD, and consolidate current evidence of this complex interplay, whilst highlighting gaps in the literature. We focus on diet as one of the major modulators of the gut microbiota, and explain key microbial-derived metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide) as potential mediators of the communication between the gut and peripheral organs such as the heart, arteries, kidneys, and the brain via the immune system. Finally, we explore the dual role of both the gut microbiome and the immune system, and how they work together to not only contribute, but also mitigate hypertension and CVD.

A Two-Faced Gut Microbiome: Butyrogenic and Proinflammatory Bacteria Predominate in the Intestinal Milieu of People Living with HIV from Western Mexico.

HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.

Prevotella enterotype associates with diets supporting acidic faecal pH and production of propionic acid by microbiota.

Metabolism of dietary fibres by colon microbiota plays an important role for human health. Personal data from a nutrition study (57 subjects) were analysed to elucidate quantitative associations between the diet, faecal microbiome, organic acid concentrations and pH. Ratios of the predominant acids acetate, butyrate and propionate ranged from 1:0.67:0.27 to 1:0.17:0.36. Pectin-rich diets resulted in higher faecal acetate concentrations. Negative correlation between faecal pH and BSS was observed. Higher faecal pH and lower acid concentrations were related to the higher abundance of amino acid degrading Clostridium, Odoribacter and Eubacterium coprostanoligenes, which are weak carbohydrate fermenting taxa. Propionic acid correlated especially to high abundance of Prevotella and low abundance of proteobacteria. The acetate to propionate ratio of the Prevotella enterotype was about half of that of the Bacteroides enterotype. Based on the results we suggest the measurement of faecal pH and organic acid composition for research and diagnostic purposes.

Acinetobacter in fresh faecal samples is related to sperm motility: A case report in Piétrain boars housed on different deep-litter bedding materials.

The swine gastrointestinal tract contains a great variety of microbes, forming a complex and dynamic ecosystem. Various internal and external factors (e.g. age, breed and diet) may influence its composition. This study aimed to investigate the gut microbial diversity of German Piétrain boars housed on different deep-litter bedding materials (regional wood shavings, linen, hemp, spelt husks, and wood shavings) via 16S-rDNA sequencing. Additionally, short-chain fatty acids were analysed using gas chromatography. Fresh faecal samples (n = 80) from 40 Piétrain boars were collected twice during the trial. Although it can be assumed that boars ingest bedding orally, no differences in the microbiome composition could be found. The main phyla were Firmicutes and Bacteroides. Acinetobacter was identified as a biomarker for sperm quality differences (total sperm motility) in breeding boars.

Modulation of multiple sclerosis risk and pathogenesis by the gut microbiota: Complex interactions between host genetics, bacterial metabolism, and diet.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, affecting nearly 2 million people worldwide. The etiology of MS is multifactorial: Approximately 30% of the MS risk is genetic, which implies that the remaining ~70% is environmental, with a number of factors proposed. One recently implicated risk factor for MS is the composition of the gut microbiome. Numerous case-control studies have identified changes in gut microbiota composition of people with MS (pwMS) compared with healthy control individuals, and more recent studies in animal models have begun to identify the causative microbes and underlying mechanisms. Here, we review some of these mechanisms, with a specific focus on the role of host genetic variation, dietary inputs, and gut microbial metabolism, with a particular emphasis on short-chain fatty acid and tryptophan metabolism. We put forward a model where, in an individual genetically susceptible to MS, the gut microbiota and diet can synergize as potent environmental modifiers of disease risk and possibly progression, with diet-dependent gut microbial metabolites serving as a key mechanism. We also propose that specific microbial taxa may have divergent effects in individuals carrying distinct variants of MS risk alleles or other polymorphisms, as a consequence of host gene-by-gut microbiota interactions. Finally, we also propose that the effects of specific microbial taxa, especially those that exert their effects through metabolites, are highly dependent on the host dietary intake. What emerges is a complex multifaceted interaction that has been challenging to disentangle in human studies, contributing to the divergence of findings across heterogeneous cohorts with differing geography, dietary preferences, and genetics. Nonetheless, this provides a complex and individualized, yet tractable, model of how the gut microbiota regulate susceptibility to MS, and potentially progression of this disease. Thus, we conclude that prophylactic or therapeutic modulation of the gut microbiome to prevent or treat MS will require a careful and personalized consideration of host genetics, baseline gut microbiota composition, and dietary inputs.