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.

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.

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.

Prebiotic characteristics of degraded polysaccharides from Acanthopanax senticosus polysaccharide on broilers gut microbiota based on in vitro digestion and fecal fermentation.

This study aimed to evaluate the effect of low molecular weight Acanthopanax polysaccharides on simulated digestion, probiotics, and intestinal flora of broilers in vitro. The experiments were carried out by H2O2-Vc degradation of Acanthopanax polysaccharides, in vitro simulated digestion to evaluate the digestive performance of polysaccharides with different molecular weights, in vitro probiotic evaluation of the probiotic effect of polysaccharides on lactobacilli and bifidobacteria, in vitro anaerobic fermentation and high-throughput sequencing of 16S rRNA genes to study the impact of Acanthopanax polysaccharides on the intestinal flora of broilers, and the effect of Acanthopanax polysaccharides on the short-chain fatty acids of intestines were determined by GC-MS method. The results showed that the molecular weight of Acanthopanax polysaccharide (ASPS) was 9,543 Da, and the molecular weights of polysaccharides ASPS-1 and ASPS-2 were reduced to 4,288 Da and 3,822 Da after degradation, and the particle sizes, PDIs, and viscosities were also significantly decreased. ASPS-1 has anti-digestive properties and better in vitro probiotic properties. The addition of ASPS-1 regulates the structure of intestinal microorganisms by regulating fecalibacterium to produce short-chain fatty acids, promoting the colonization of beneficial bacteria such as fecalibacterium, paraprevotella and diminishing the prevalence of detrimental bacteria such as Fusobacteria. Interestingly the ASPS-1 group found higher levels of Paraprevotella, which degraded trypsin in the gut, reducing inflammation, acted as a gut protector, and was influential in increasing the levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and total SCFAs in the fermented feces. Therefore, the degraded ASPS-1 can better regulate the structure of intestinal flora and promote the production of SCFAs, creating possibilities for its use as a potential prebiotic, which is conducive to the intestinal health of poultry.

Short-chain fatty acids induced lung tumor cell death and increased peripheral blood CD4+ T cells in NSCLC and control patients ex vivo.

Background: Despite therapy advances, one of the leading causes of cancer deaths still remains lung cancer. To improve current treatments or prevent non-small cell lung cancer (NSCLC), the role of the nutrition in cancer onset and progression needs to be understood in more detail. While in colorectal cancer, the influence of local microbiota derived SCFAs have been well investigated, the influence of SCFA on lung cancer cells via peripheral blood immune system should be investigated more deeply. In this respect, nutrients absorbed via the gut might affect the tumor microenvironment (TME) and thus play an important role in tumor cell growth. Objective: This study focuses on the impact of the short-chain fatty acid (SCFA) Sodium Butyrate (SB), on lung cancer cell survival. We previously described a pro-tumoral role of glucose on A549 lung adenocarcinoma cell line. In this study, we wanted to know if SB would counteract the effect of glucose and thus cultured A549 and H520 in vitro with and without SB in the presence or absence of glucose and investigated how the treatment with SB affects the survival of lung cancer cells and its influence on immune cells fighting against lung cancer. Methods: In this study, we performed cell culture experiments with A549, H520 and NSCLC-patient-derived epithelial cells under different SB levels. To investigate the influence on the immune system, we performed in vitro culture of peripheral mononuclear blood cells (PBMC) from control, smoker and lung cancer patients with increasing SB concentrations. Results: To investigate the effect of SB on lung tumor cells, we first analyzed the effect of 6 different concentrations of SB on A549 cells at 48 and 72 hours cell culture. Here we found that, SB treatment reduced lung cancer cell survival in a concentration dependent manner. We next focused our deeper analysis on the two concentrations, which caused the maximal reduction in cell survival. Here, we observed that SB led to cell cycle arrest and induced early apoptosis in A549 lung cancer cells. The expression of cell cycle regulatory proteins and A549 lung cancer stem cell markers (CD90) was induced. Additionally, this study explored the role of interferon-gamma (IFN-γ) and its receptor (IFN-γ-R1) in combination with SB treatment, revealing that, although IFN-γ-R1 expression was increased, IFN-γ did not affect the efficacy of SB in reducing tumor cell viability. Furthermore, we examined the effects of SB on immune cells, specifically CD8+ T cells and natural killer (NK) cells from healthy individuals, smokers, and NSCLC patients. SB treatment resulted in a decreased production of IFN-γ and granzyme B in CD8+ T cells and NK cells. Moreover, SB induced IFN-γ-R1 in NK cells and CD4+ T cells in the absence of glucose both in PBMCs from controls and NSCLC subjects. Conclusion: Overall, this study highlights the potential of SB in inhibiting lung cancer cell growth, triggering apoptosis, inducing cell cycle arrest, and modulating immune responses by activating peripheral blood CD4+ T cells while selectively inducing IFN-γ-R1 in NK cells in peripheral blood and inhibiting peripheral blood CD8+ T cells and NK cells. Thus, understanding the mechanisms of action of SB in the TME and its influence on the immune system provide valuable insights of potentially considering SB as a candidate for adjunctive therapies in NSCLC.

A systematic review of the beneficial effects of prebiotics, probiotics, and synbiotics on ADHD.

BACKGROUND: Children with attention deficit hyperactivity disorder (ADHD) may benefit from probiotics and prebiotics, but the effects are unclear. To determine whether probiotics and prebiotics affect children with ADHD, a systematic review was conducted. METHODS: The present systematic review analyzed cohort studies and randomized controlled trials that examined whether prebiotics and probiotics are associated with ADHD. Seven randomized controlled trials and two cohort studies met our inclusion criteria. RESULTS: Research on Lactobacillus rhamnosus GG (LGG) probiotic supplementation showed that children with ADHD had better emotional, physical, social, and school functioning, and a higher health-related quality of life compared to the placebo group. The studies also showed that Synbiotic 2000 reduces markers of intestinal and vascular inflammation in children with ADHD, in part through increasing SCFA levels. CONCLUSION: The use of probiotics and prebiotics as adjuvants therapy in patients with ADHD is beneficial. Further studies with longer duration, including more participants and a variety of age groups, and using various evaluation techniques such as in vivo observation are required to examine the effects of prebiotics and probiotics on ADHD.

Short-chain fatty acids modulate the IPEC-J2 cell response to pathogenic E. coli LPS-activated PBMC.

Intestinal disorders can affect pigs of any age, especially when animals are young and more susceptible to infections and environmental stressors. For instance, pathogenic E. coli can alter intestinal functions, thus leading to altered nutrient adsorption by interacting with local cells through lipopolysaccharide (LPS). Among several compounds studied to counteract the negative effects on the intestine, short-chain fatty acids (SCFA) were demonstrated to exert beneficial effects on gut epithelial cells and resident immune cells. In this study, acetate and propionate were tested for their beneficial effects in a co-culture model of IPEC-J2 and porcine PBMC pre-stimulated with LPS from E. coli 0111:B4 aimed at mimicking the interaction between intestinal cells and immune cells in an inflammatory/activated status. IPEC-J2 viability was partially reduced when co-cultured with activated PBMC and nitric oxide concentration increased. IPEC-J2 up-regulated innate and inflammatory markers, namely BD-1, TLR-4, IL-8, TNF-α, NF-κB, and TGF-ß. Acetate and propionate positively modulated the inflammatory condition by sustaining cell viability, reducing the oxidative stress, and down-regulating the expression of inflammatory mediators. TNF-α expression and secretion showed an opposite effect in IPEC-J2 depending on the extent of LPS stimulation of PBMC and TGF-ß modulation. Therefore, SCFA proved to mediate a differential effect depending on the degree and duration of inflammation. The expression of the tight junction proteins (TJp) claudin-4 and zonula occludens-1 was up-regulated by LPS while SCFA influenced TJp with a different kinetics depending on PBMC stimulation. The co-culture model of IPEC-J2 and LPS-activated PBMC proved to be feasible to address the modulation of markers related to anti-bacterial immunity and inflammation, and intestinal epithelial barrier integrity, which are involved in the in vivo responsiveness and plasticity to infections.

Microbiome interactions with different risk factors in development of myocardial infarction.

Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.

Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother's obesity as potentially environmental factors of ASD. The purpose of this review is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

PNPLA3 Genotype and Dietary Fat Modify Concentrations of Plasma and Fecal Short Chain Fatty Acids and Plasma Branched-Chain Amino Acids.

The GG genotype of the Patatin-like phosphatase domain-containing 3 (PNPLA3), dietary fat, short-chain fatty acids (SCFA) and branched-chain amino acids (BCAA) are linked with non-alcoholic fatty liver disease. We studied the impact of the quality of dietary fat on plasma (p) and fecal (f) SCFA and p-BCAA in men homozygous for the PNPLA3 rs738409 variant (I148M). Eighty-eight randomly assigned men (age 67.8 ± 4.3 years, body mass index 27.1 ± 2.5 kg/m2) participated in a 12-week diet intervention. The recommended diet (RD) group followed the National and Nordic nutrition recommendations for fat intake. The average diet (AD) group followed the average fat intake in Finland. The intervention resulted in a decrease in total p-SCFAs and iso-butyric acid in the RD group (p = 0.041 and p = 0.002). Valeric acid (p-VA) increased in participants with the GG genotype regardless of the diet (RD, 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.005 and AD, 3.8 ± 0.3 to 9.7 ± 8.5 µmol/g, p = 0.015). Also, genotype relation to p-VA was seen statistically significantly in the RD group (CC: 3.7 ± 0.4 to 4.2 ± 1.7 µmol/g and GG: 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.0026 for time and p = 0.004 for time and genotype). P-VA, unlike any other SCFA, correlated positively with plasma gamma-glutamyl transferase (r = 0.240, p = 0.025). Total p-BCAAs concentration changed in the AD group comparing PNPLA3 CC and GG genotypes (CC: 612 ± 184 to 532 ± 149 µmol/g and GG: 587 ± 182 to 590 ± 130 µmol/g, p = 0.015 for time). Valine decreased in the RD group (p = 0.009), and leucine decreased in the AD group (p = 0.043). RD decreased total fecal SCFA, acetic acid (f-AA), and butyric acid (f-BA) in those with CC genotype (p = 0.006, 0.013 and 0.005, respectively). Our results suggest that the PNPLA3 genotype modifies the effect of dietary fat modification for p-VA, total f-SCFA, f-AA and f-BA, and total p-BCAA.

Lactobacillus rhamnosus (LR) ameliorates pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) via targeting neutrophils.

Pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure associated with high mortality. Despite progress in our understanding of the pathological mechanism causing the crippling illness, there are currently no targeted pharmaceutical treatments available for it. Recent discoveries have emphasized the existence of a potential nexus between gut and lung health fueling novel approaches including probiotics for the treatment of ARDS. We thus investigated the prophylactic-potential of Lactobacillus rhamnosus-(LR) in lipopolysaccharide (LPS)-induced pulmonary and cecal ligation puncture (CLP) induced extrapulmonary ARDS mice. Our in-vivo findings revealed that pretreatment with LR significantly ameliorated vascular-permeability (edema) of the lungs via modulating the neutrophils along with significantly reducing the expression of inflammatory-cytokines in the BALF, lungs and serum in both pulmonary and extrapulmonary mice-models. Interestingly, our ex-vivo immunofluorescence and flow cytometric data suggested that mechanistically LR via short chain fatty acids (butyrate being the most potent and efficient in ameliorating the pathophysiology of both pulmonary and extra-pulmonary ARDS) targets the phagocytic and neutrophils extracellular traps (NETs) releasing potential of neutrophils. Moreover, our in-vivo data further corroborated our ex-vivo findings and suggested that butyrate exhibits enhanced potential in ameliorating the pathophysiology of ARDS via reducing the infiltration of neutrophils into the lungs. Altogether, our study establishes the prophylactic role of LR and its associated metabolites in the prevention and management of both pulmonary and extrapulmonary ARDS via targeting neutrophils.

Carbon dioxide and trace oxygen concentrations impact growth and product formation of the gut bacterium Phocaeicola vulgatus.

BACKGROUND: The promising yet barely investigated anaerobic species Phocaeicola vulgatus (formerly Bacteroides vulgatus) plays a vital role for human gut health and effectively produces organic acids. Among them is succinate, a building block for high-value-added chemicals. Cultivating anaerobic bacteria is challenging, and a detailed understanding of P. vulgatus growth and metabolism is required to improve succinate production. One significant aspect is the influence of different gas concentrations. CO2 is required for the growth of P. vulgatus. However, it is a greenhouse gas that should not be wasted. Another highly interesting aspect is the sensitivity of P. vulgatus towards O2. In this work, the effects of varying concentrations of both gases were studied in the in-house developed Respiratory Activity MOnitoring System (RAMOS), which provides online monitoring of CO2, O2, and pressure under gassed conditions. The RAMOS was combined with a gas mixing system to test CO2 and O2 concentrations in a range of 0.25-15.0 vol% and 0.0-2.5 vol%, respectively. RESULTS: Changing the CO2 concentration in the gas supply revealed a CO2 optimum of 3.0 vol% for total organic acid production and 15.0 vol% for succinate production. It was demonstrated that the organic acid composition changed depending on the CO2 concentration. Furthermore, unrestricted growth of P. vulgatus up to an O2 concentration of 0.7 vol% in the gas supply was proven. The viability decreased rapidly at concentrations larger than or equal to 1.3 vol% O2. CONCLUSIONS: The study showed that P. vulgatus requires little CO2, has a distinct O2 tolerance and is therefore well suited for industrial applications.

Evidence of the Beneficial Impact of Three Probiotic-Based Food Supplements on the Composition and Metabolic Activity of the Intestinal Microbiota in Healthy Individuals: An Ex Vivo Study.

Scientific evidence has increasingly supported the beneficial effects of probiotic-based food supplements on human intestinal health. This ex vivo study investigated the effects on the composition and metabolic activity of the intestinal microbiota of three probiotic-based food supplements, containing, respectively, (1) Bifidobacterium longum ES1, (2) Lactobacillus acidophilus NCFM®, and (3) a combination of L. acidophilus NCFM®, Lactobacillus paracasei Lpc-37™, Bifidobacterium lactis Bi-07™, and Bifidobacterium lactis Bl-04™. This study employed fecal samples from six healthy donors, inoculated in a Colon-on-a-plate® system. After 48 h of exposure or non-exposure to the food supplements, the effects were measured on the overall microbial fermentation (pH), changes in microbial metabolic activity through the production of short-chain and branched-chain fatty acids (SCFAs and BCFAs), ammonium, lactate, and microbial composition. The strongest effect on the fermentation process was observed for the combined formulation probiotics, characterized by the significant stimulation of butyrate production, a significant reduction in BCFAs and ammonium in all donors, and a significant stimulatory effect on bifidobacteria and lactobacilli growth. Our findings suggest that the combined formulation probiotics significantly impact the intestinal microbiome of the healthy individuals, showing changes in metabolic activity and microbial abundance as the health benefit endpoint.

Role of mesenchymal stem cells and short chain fatty acids in allergy: A prophylactic therapy for future.

Allergic diseases are broadly classified as IgE-mediated type-I hypersensitivity immune reactions due to exposure to typically harmless substances known as allergens. These allergenic substances activate antigen presenting cells, which further triggers T-helper 2 cells immune response and class switch B-cells for synthesis of allergen-specific IgE, followed by classical activation of inflammatory mast cells and eosinophils, which releases preformed mediators involved in the cascade of allergic symptoms. However, the role of Mesenchymal stem cells (MSCs) in tissue repair ability and immunomodulation, makes them as an appropriate tool for treatment of various allergic diseases. Several clinical and preclinical studies show that MSCs could be a promising alternative therapy to allergic diseases. Further, short chain fatty acids, produced from gut microbes by breaking down complex fibre-rich foods, acts through G-coupled receptor mediated activation of MSCs, and their role as key players involved in amelioration of allergic inflammation needs further investigation. Therefore, there is a need for understating the role of SCFAs on the activation of MSCs, which might shed light on the development of new therapeutic regime in allergy treatment. In summary, this review focuses on the underlying of therapeutic role of MSCs in different allergic diseases and the prospects of SCFA and MSC therapy.

A major mechanism for immunomodulation: Dietary fibres and acid metabolites.

Diet and the gut microbiota have a profound influence on physiology and health, however, mechanisms are still emerging. Here we outline several pathways that gut microbiota products, particularly short-chain fatty acids (SCFAs), use to maintain gut and immune homeostasis. Dietary fibre is fermented by the gut microbiota in the colon, and large quantities of SCFAs such as acetate, propionate, and butyrate are produced. Dietary fibre and SCFAs enhance epithelial integrity and thereby limit systemic endotoxemia. Moreover, SCFAs inhibit histone deacetylases (HDAC), and thereby affect gene transcription. SCFAs also bind to 'metabolite-sensing' G-protein coupled receptors (GPCRs) such as GPR43, which promotes immune homeostasis. The enormous amounts of SCFAs produced in the colon are sufficient to lower pH, which affects the function of proton sensors such as GPR65 expressed on the gut epithelium and immune cells. GPR65 is an anti-inflammatory Gαs-coupled receptor, which leads to the inhibition of inflammatory cytokines. The importance of GPR65 in inflammatory diseases is underscored by genetics associated with the missense variant I231L (rs3742704), which is associated with human inflammatory bowel disease, atopic dermatitis, and asthma. There is enormous scope to manipulate these pathways using specialized diets that release very high amounts of specific SCFAs in the gut, and we believe that therapies that rely on chemically modified foods is a promising approach. Such an approach includes high SCFA-producing diets, which we have shown to decrease numerous inflammatory western diseases in mouse models. These diets operate at many levels - increased gut integrity, changes to the gut microbiome, and promotion of immune homeostasis, which represents a new and highly promising way to prevent or treat human disease.

Can butyrate prevent colon cancer? The AusFAP study: A randomised, crossover clinical trial.

Increased colonic butyrate from microbial fermentation of fibre may protect from colorectal cancer (CRC). Dietary butyrylated high amylose maize starch (HAMSB) delivers butyrate to the large bowel. The objective of this clinical trial (AusFAP) is to evaluate potential chemoprotective effects of HAMSB on polyposis in individuals with a genetic form of colon cancer, Familial Adenomatous Polyposis (FAP). The study is a multi-site, double blind, randomised, placebo-controlled crossover trial undertaken at major hospitals in Australia. After a baseline endoscopy participants consume either 40g/day of HAMSB or placebo (low amylose maize) starch for 26 weeks. After another endoscopic examination participants consume the alternate starch for 26 weeks. A third endoscopy at 52 weeks is followed by 26 weeks' washout and a final endoscopy at 78 weeks. Primary outcome measure is the global large bowel polyp number. Secondary measures include global polyp size counts, and number and size of polyps at two tattoo sites: one cleared of polyps at baseline, and another safely chosen with polyps left in situ during the study. Other secondary outcome measures include the effects of intervention on cellular proliferation in colonic biopsies, faecal measures including short chain fatty acid concentrations, and participants' dietary intakes. Generalized linear mixed models analysis will be used to estimate differences in primary outcomes between intervention and placebo periods. This study represents the first clinical evaluation of the effects of increased colonic butyrate on polyp burden in FAP which, if effective, may translate to lower risk of sporadic CRC in the community. Australian New Zealand Clinical Trials Registry Number: 12612000804886.

The gut microbiome in intravenous immunoglobulin-treated chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: The gut microbiome is involved in autoimmunity. Data on its composition in chronic inflammatory demyelinating polyneuropathy (CIDP), the most common chronic autoimmune disorder of peripheral nerves, are currently lacking. METHODS: In this monocentric exploratory pilot study, stool samples were prospectively collected from 16 CIDP patients (mean age 58 ± 10 years, 25% female) before and 1 week after administration of intravenous immunoglobulin (IVIg). Gut microbiota were analyzed via bacterial 16S rRNA gene sequencing and compared to 15 age-matched healthy subjects (mean age 59 ± 15 years, 66% female). RESULTS: The gut microbiota of CIDP patients showed an increased alpha-diversity (p = 0.005) and enrichment of Firmicutes, such as Blautia (p = 0.0004), Eubacterium hallii (p = 0.0004), or Ruminococcus torques (p = 0.03), and of Actinobacteriota (p = 0.03) compared to healthy subjects. IVIg administration did not alter the gut microbiome composition in CIDP in this short-term observation (p = 0.95). CONCLUSIONS: The gut microbiome in IVIg-treated CIDP shows distinct features, with increased bacterial diversity and enrichment of short-chain fatty acid producing Firmicutes. IVIg had no short-term impact on the gut microbiome in CIDP patients. As the main limitation of this exploratory pilot study was small cohort size, future studies also including therapy-naïve patients are warranted to verify our findings and to explore the impact of long-term IVIg treatment on the gut microbiome in CIDP.

Impact of cafeteria diet and n3 supplementation on the intestinal microbiota, fatty acids levels, neuroinflammatory markers and social memory in male rats.

OBJECTIVE: To assess the effects of omega-3 (n3) supplementation on intestinal microbiota, fatty acids profile, neuroinflammation, and social memory of cafeteria diet (CAF)-fed rats. METHODS: Male Wistar rats were fed with CAF for 20 weeks. Omega-3 (500 mg/kg/day) was supplemented between the 16th and 20th week. Colon morphology, intestinal microbiota composition, short-chain fatty acids (SCFA) and lipopolysaccharide (LPS) in the plasma, fatty acids profile, TLR-4 and claudin-5 expressions in the brain, and social memory were investigated. RESULTS: CAF reduced colon length, crypts' depth, and microbiota diversity, while n3 increased the Firmicutes/Bacteroidetes ratio. CAF increased SCFA plasma levels, but n3 reduced butyrate and isobutyrate in obese rats. LPS was increased in CAF-fed rats, and n3 decreased its levels. In the cerebral cortex, n3 increased caprylic, palmitic, stearic, tricosanoic, lignoceric, myristoleic, and linoleic acids. CAF increased palmitic acid and TLR-4 expression in the cerebral cortex while decreasing claudin-5 in the hippocampus. In the social memory test, CAF-fed animals showed greater social interaction with no effect of n3. CONCLUSIONS: The lack of n3 effect in some of the evaluated parameters may be due to the severity of the obesity caused by CAF. However, n3 reduced LPS levels, suggesting its ability to reverse endotoxemia.

Butyrate: Connecting the gut-lung axis to the management of pulmonary disorders.

Short-chain fatty acids (SCFAs) are metabolites released by bacterial components of the microbiota. These molecules have a wide range of effects in the microbiota itself, but also in host cells in which they are known for contributing to the regulation of cell metabolism, barrier function, and immunological responses. Recent studies indicate that these molecules are important players in the gut-lung axis and highlight the possibility of using strategies that alter their intestinal production to prevent or treat distinct lung inflammatory diseases. Here, we review the effects of the SCFA butyrate and its derivatives in vitro and in vivo on murine models of respiratory disorders, besides discussing the potential therapeutic use of butyrate and the other SCFAs in lung diseases.