Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Effect of Lactobacillus reuteri NCIMB 30351 drops on symptoms of infantile functional gastrointestinal disorders and gut microbiota in early infants: Results from a randomized, placebo-controlled clinical trial.

Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, representing one of the causes of significant parental anxiety, lead to a significant strain on the healthcare resources. In this study, we aimed to evaluate the effects of Lactobacillus reuteri drops (L. reuteri NCIMB 30351) on the symptoms of infantile colic, constipation, diarrhea, and gastroesophageal reflux, as well as on the levels of intestinal microbiota in full-term newborns during the first months of life. A randomized, placebo-controlled, single-masked (blinded), post-marketing clinical study was conducted in two clinical units-Children's City Clinical Hospital of Moscow and Medical Center "St. Andrew's Hospitals-NEBOLIT" from March 2020 to May 2022 in 90 infants aged from 1 to 4 months (mean age (± SD) 12.3 ± 5.09 weeks; 53.3% females, 46.7% males). Patients with colic, regurgitation (single symptom or combination of several symptoms), and constipation or diarrhea were randomly allocated in two parallel arms to receive either 5 drops (2 × 108 colony forming unit) of L. reuteri NCIMB 30351 (n = 60) or masked placebo (n = 30) for 25 consecutive days. Two treatment arms had equal numbers of patients with constipation and diarrhea (n = 30 each). Daily crying times and their duration, evacuations, and regurgitations were recorded in a structured diary. The levels of gut microbiota were analyzed by deep sequencing of bacterial 16S rRNA gene. Infants with colic receiving supplementary L. reuteri NCIMB 30351 for 25 days had significant reduction in the numbers of colic (change from baseline - 6.3 (7.34) vs - 3.0 (7.29) in placebo, P < 0.05) and numbers of crying cases and mean duration of crying (decrease from baseline - 144 (70.7) minutes, lower in the diarrhea subgroup than in constipation infants, compared with - 80 (58.9) in placebo, P < 0.0001), as well as regurgitation numbers (decreased by - 4.8 (2.49) with L. reuteri vs - 3 (7.74) with placebo). We also observed increased numbers of evacuations in infants with constipation (L. reuteri 2.2 (2.4) vs 0.9 (1.06) in placebo, P < 0.05). There was a remarkable reduction of evacuations in infants with diarrhea, while not statistically significant. The analysis of bacterial 16S rRNA gene in the collected samples showed that L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes. Additional in vitro test for formation of Clostridium colonies in the presence of the probiotic demonstrated that L. reuteri effectively inhibits the growth of pathogenic Clostridium species. No adverse events were reported in this study.   Conclusion: The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. Our results suggest that L. reuteri NCIMB 30351 represents a safe and effective treatment for colic in newborns.  Trial registration: ClinicalTrials.gov : NCT04262648. What is Known: • Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, represent one of the causes of significant parental anxiety. • A number of studies have shown that both the composition and diversity of the intestinal microbiota play important roles in the development and function of the gastrointestinal tract. What is New: • The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. • L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes in gut microbiota.

Influence of Helicobacter pylori Infection and Eradication on Small Intestinal Bacterial Overgrowth and Abdominal Symptoms.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and small intestinal bacterial overgrowth (SIBO) has attracted attention recently. AIMS: To analyze the influence of H. pylori infection and eradication on SIBO, IMO, and abdominal symptoms. METHODS: Patients with gastrointestinal symptoms were tested for 13C urea breath test and if positive, treated with bismuth-based quadruple therapy. Lactulose hydrogen methane breath test (HMBT) was performed and symptoms were assessed using gastrointestinal symptom rating scale (GSRS) before and 6 weeks after eradication. RESULTS: Of the 102 subjects, 53 were H. pylori positive. The prevalence of SIBO and IMO were higher in patients with H. pylori infection than in those without infection (49.1% vs 24.5%, P = 0.019 for SIBO; 24.5% vs 8.2%, P = 0.027 for IMO). GSRS scores were similar between H. pylori-infected and uninfected patients (2 (IQR: 1;3) vs 2 (IQR: 1;2), P = 0.211). Patients with SIBO or IMO presented higher GSRS scores than patients with both SIBO and IMO negative (2 (IQR: 2;3), 2 (IQR: 2;3) vs 2 (IQR: 1;2), P = 0.011, 0.001, respectively). For the 50 patients who successfully eradicated H. pylori, the response rates for SIBO and IMO were 66.7% and 76.9%, respectively. GSRS scores also significantly decreased (2 (IQR: 1;3) to 0 (IQR: 0;1), P < 0.001) after eradication. CONCLUSION: Helicobacter pylori infection was associated with higher prevalence of SIBO and IMO, both of which led to more pronounced abdominal symptoms. H. pylori eradication also achieved therapeutic effects on SIBO and IMO, accompanied by relief of abdominal symptoms.

Semi-quantitative assessment of gastrointestinal viruses in stool samples with Seegene Allplex gastrointestinal panel assays: a solution to the interpretation problem of multiple pathogen detection?

PURPOSE: The aim of the study was to determine and evaluate the clinical usefulness of pathogen specific semi-quantitative cut-offs in stool samples with multiple pathogen detections. METHODS: The PCR (Seegene Allplex Gastrointestinal Virus Assay) data from 4527 positive samples received over 16 months were retrospectively analyzed to investigate the distribution of the Ct values of each individual viral pathogen. By using interquartile ranges for each viral pathogen, pathogen specific semi-quantitative cut-offs were determined. RESULTS: After a thorough analysis of the Ct values, a well-founded decision to exclude all results with a Ct value higher than 35 was made. This approach made it possible to generate a more nuanced report and to facilitate clinical interpretation in case of mixed infections by linking a lower Ct value of a pathogen to a greater likelihood of being a relevant causative pathogen. Moreover, not reporting viral pathogens with a Ct value higher than 35 led to a significant reduction (p < 0.0001) of reported mixed infections compared to oversimplified qualitative or qualitative reporting. CONCLUSION: By omitting very high Ct values and reporting semi-quantitatively, value was added to the syndromic reports, leading to an easier to read lab report, especially in mixed infections.

Advancing the fitness of gut commensal bacteria.

Nutrient starvation of beneficial bacteria helps them colonize the human gut.

Microbiota intestinal y cólicos infantiles: ¿hay lugar para los prebióticos, probióticos y posbióticos? / Gut Microbiota and Infant Colic: is there a Place for Prebiotics, Probiotics, and Postbiotics?

El consumo de probióticos, prebióticos y posbióticos, o su combinación, puede contribuir a mantener una microbiota intestinal saludable ya que permite la regulación de su disbiosis en el caso de algunas enfermedades o trastornos, principalmente en los trastornos gastrointestinales funcionales (TGIF). El microbioma intestinal es protagonista esencial en la fisiopatología de los TGIF a través de sus funciones metabólicas y nutricionales, el mantenimiento de la integridad de la mucosa intestinal y la regulación de la respuesta inmunitaria. Las investigaciones realizadas hasta la fecha indican que los probióticos, prebióticos y posbióticos pueden tener efectos inmunomoduladores directos y clínicamente relevantes. Existen pruebas del uso de esta familia de bióticos en individuos sanos para mejorar la salud general y aliviar los síntomas en una serie de enfermedades como los cólicos infantiles. La colonización y establecimiento de la microbiota comienza en el momento del nacimiento; los primeros 2-3 años de vida son fundamentales para el desarrollo de una comunidad microbiana abundante y diversa. Diversos estudios científicos realizados mediante técnicas tradicionales dependientes de cultivo y más recientemente por técnicas moleculares han observado diferencias en las poblaciones bacterianas de bebés sanos y aquellos que sufren TGIF, estos últimos caracterizados por un aumento de especies patógenas y una menor población de bifidobacterias y lactobacilos, en comparación con los primeros. En tal contexto, se considera que la microbiota intestinal como protagonista en el desarrollo de esos trastornos, entre ellos los cólicos infantiles, a través de sus funciones metabólicas, nutricionales, de mantenimiento de la integridad de la mucosa intestinal y regulación de la respuesta inmunitaria. Esto ha abierto la puerta al estudio de la utilización de prebióticos, probióticos y posbióticos en el tratamiento y/o prevención de los TGIF infantiles. El parto vaginal y de término así como la lactancia son fundamentales en la constitución de una microbiota saludable. Como herramientas de apoyo, existen estudios de eficacia que sustentan la administración de esta familia de bióticos, principalmente en los casos en que la lactancia no sea posible o esté limitada. (AU)

The consumption of probiotics, prebiotics, and postbiotics, or a combination of them, can contribute to maintaining a healthy intestinal microbiota as it allows the regulation of its dysbiosis in the case of some diseases or disorders, mainly in functional gastrointestinal disorders (FGIDs). The gut microbiome is an essential player in the pathophysiology of FGIDs through its metabolic and nutritional functions, the maintenance of intestinal mucosal integrity, and the regulation of the immune response. Research results thus far indicate that probiotics, prebiotics, and postbiotics may have direct and clinically relevant immunomodulatory effects. There is evidence regarding the prescription of this family of biotics in healthy individuals to improve overall health and alleviate symptoms in many conditions like infantile colic. The colonization and microbiota establishment begins at birth; the first 2-3 years of life are critical for developing an abundant and diverse microbial community. Several scientific studies performed by traditional culture-dependent techniques and more recently by molecular techniques have observed differences in the bacterial populations of healthy infants and those suffering from FGIDs, the latter characterized by an increase in pathogenic species and a lower population of bifidobacteria and lactobacilli, compared to the former. In this context, the intestinal microbiota plays a leading role in the onset of these disorders, including infantile colic, through its metabolic and nutritional functions, maintenance of the integrity of the intestinal mucosa, and regulation of the immune response. That has opened the door to the study of prebiotics, probiotics, and postbiotics usage in the treatment and or prevention of infantile FGIDs. Vaginal and term delivery and breastfeeding are fundamental in the constitution of a healthy microbiota. As supportive tools, there are efficacy studies that support the administration of this family of biotics, mainly in cases where lactation is not possible or is limited.

Quantitative microbial risk assessment of the gastrointestinal risks to swimmers at Southeast Asian urban beaches using site-specific and combined autochthonous and fecal bacteria exposure data.

Recreational exposure to microbial pollution at urban beaches poses a health risk to beachgoers. The accurate quantification of such risks is crucial in managing beaches effectively and establishing warning guidelines. In this study, we employed a quantitative microbial risk assessment (QMRA) framework to assess marine water quality and estimate the risks associated with Vibrio parahaemolyticus, an autochthonous pathogen that causes gastrointestinal illnesses, and enterococci, a traditional fecal bacteria indicator. The microbial contamination levels of V. parahaemolyticus and enterococci were determined from 48 water samples collected at two beaches in Thailand during dry and wet seasons. The accidentally ingested water volumes were obtained through a survey involving 438 respondents. The probability of illness (Pill) was estimated using dose-response models and Monte Carlo simulation. The results revealed that enterococci posed a higher risk of illness than V. parahaemolyticus at all seven study sites. The median combined gastrointestinal (GI) risk from both bacteria at all sites met the US EPA risk benchmark of 0.036 and the 0.05 benchmark set by the WHO, but the 95th percentile risk data at all sites exceeded the benchmarks. This emphasizes the need for the continuous monitoring and management of microbial pollution at these sites. The site-specific exposure data showed higher estimated risks with increased variations compared to the WHO-referenced values, which highlights the significance of locally measured microbial concentrations and survey exposure data to avoid underestimation. Estimating the risks from recreational exposure to waterborne bacteria can inform beach management policies aimed at reducing public health risks to swimmers. The study findings improve the understanding of the risks associated with water recreation activities at Southeast Asian beaches and offer valuable insights for the development of water quality guidelines, which are crucial for the sustainable development of the blue economy.

Altered Gut Microbiota as Potential Biomarkers for Autism Spectrum Disorder in Early Childhood.

Gastrointestinal (GI) disorders are widely recorded in autism spectrum disorder (ASD), and ASD with GI symptoms is a vital subtype of this disease. Growing evidence suggests altered gut microbiota biomarkers in ASD, but little is known about the gut microbiota of individuals with ASD with GI Symptoms, particularly in early childhood. In our study, the gut microbiota of 36 individuals with ASD along with GI symptoms and 40 typically developing (TD) children were compared using 16S rRNA gene sequencing. The microbial diversity and composition were found to differ between the two groups. Compared to TD, the gut microbiota of ASD patients with GI symptoms exhibited decreased alpha diversity and depletion of butyrate-producing bacteria (e.g., Faecalibacterium and Coprococcus). In addition, microbial functional analysis showed abnormality in several gut metabolic models and gut brain models of ASD with GI symptoms, including short-chain fatty acid (SCFA) synthesis/degradation and neurotoxin-related p-cresol degradation, which are closely associated with ASD-related behaviors in animal models. Furthermore, we constructed a Support Vector Machine classification model, which robustly discriminated individuals with ASD and GI symptoms from TD individuals in a validation set (AUC = 0.88). Our findings provide a deep insight into the roles of the disturbed gut ecosystem in individuals with ASD and GI symptoms aged 3-6 years. Our classification model supports gut microbiota as a potential biomarker for the early identification of ASD and interventions targeting particular gut-beneficial microbiota.

Plant-based diets in gastrointestinal diseases: Which evidence?

Plant-based diets (PBDs), rich in high-quality plant foods, offer multiple benefits for the overall and gastrointestinal health. Recently, it has been demostrated that the positive effects of PBDs on gastrointestinal health can be mediated by the gut microbiota, in particular, by inducing a greater diversity of bacteria. This review summarizes current knowledge on the relationship between nutrition, the gut microbiota, and host metabolic status. We discussed how dietary habits modify the composition and physiological activity of the gut microbiota and how gut dysbiosis affects the most prevalent gastrointestinal diseases, including inflammatory bowel diseases, functional bowel disorders, liver disorders, and gastrointestinal cancer. The beneficial role of PBDs is being increasingly recognized as potentially useful in the management of most diseases of the gastrointestinal tract.

Orally delivered single-domain antibodies against gastrointestinal pathogens.

Single-domain antibodies (sdAbs) are exceptionally stable fragments derived from the antigen-binding domains of immunoglobulins. They can withstand extreme pH, high temperature, and proteolysis, making them suitable for controlling gastrointestinal (GI) infections in humans and animals. sdAbs may function in their native soluble form, although different derived protein formats and the use of delivery vehicles can be useful for improved oral delivery. We discuss selected examples of the use of orally delivered sdAbs for protecting humans and animals against GI infections caused by pathogenic bacteria, viruses, and parasites. We finally provide perspectives on how sdAbs may be applied industrially and what challenges should be overcome for orally delivered sdAbs to reach the market.

Microbiota of the gastrointestinal tract: Friend or foe?

The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection. The gut microbiota encodes over 3 million genes, which is approximately 150 times more than the total number of genes present in the human genome. Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites, changes in intestinal barrier function, and inflammation and can cause the development of a wide variety of diseases, such as diabetes, obesity, gastrointestinal disorders, cardiovascular issues, neurological disorders and oncological concerns. In this review, I consider issues related to the role of the microbiome in the regulation of intestinal barrier function, its influence on physiological and pathological processes occurring in the body, and potential new therapeutic strategies aimed at restoring the gut microbiome. Herewith, it is important to understand that the gut microbiota and human body should be considered as a single biological system, where change of one element will inevitably affect its other components. Thus, the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors, the role of which has not yet been fully elucidated.

ILCs-Crucial Players in Enteric Infectious Diseases.

Research of the last decade has remarkably increased our understanding of innate lymphoid cells (ILCs). ILCs, in analogy to T helper (Th) cells and their cytokine and transcription factor profile, are categorized into three distinct populations: ILC1s express the transcription factor T-bet and secrete IFNγ, ILC2s depend on the expression of GATA-3 and release IL-5 and IL-13, and ILC3s express RORγt and secrete IL-17 and IL-22. Noteworthy, ILCs maintain a level of plasticity, depending on exposed cytokines and environmental stimuli. Furthermore, ILCs are tissue resident cells primarily localized at common entry points for pathogens such as the gut-associated lymphoid tissue (GALT). They have the unique capacity to initiate rapid responses against pathogens, provoked by changes of the cytokine profile of the respective tissue. Moreover, they regulate tissue inflammation and homeostasis. In case of intracellular pathogens entering the mucosal tissue, ILC1s respond by secreting cytokines (e.g., IFNγ) to limit the pathogen spread. Upon infection with helminths, intestinal epithelial cells produce alarmins (e.g., IL-25) and activate ILC2s to secrete IL-13, which induces differentiation of intestinal stem cells into tuft and goblet cells, important for parasite expulsion. Additionally, during bacterial infection ILC3-derived IL-22 is required for bacterial clearance by regulating antimicrobial gene expression in epithelial cells. Thus, ILCs can limit infectious diseases via secretion of inflammatory mediators and interaction with other cell types. In this review, we will address the role of ILCs during enteric infectious diseases.

Comparing the Gut Microbiome in Autism and Preclinical Models: A Systematic Review.

Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3R451C, Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of Bilophila, Clostridium, Dorea and Lactobacillus and a decrease in Blautia genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including Akkermansia, Bacteroides, Bifidobacterium, Parabacteroides and Prevotella, suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.

Analysis of global Aeromonas veronii genomes provides novel information on source of infection and virulence in human gastrointestinal diseases.

BACKGROUND: Aeromonas veronii is a Gram-negative rod-shaped motile bacterium that inhabits mainly freshwater environments. A. veronii is a pathogen of aquatic animals, causing diseases in fish. A. veronii is also an emerging human enteric pathogen, causing mainly gastroenteritis with various severities and also often being detected in patients with inflammatory bowel disease. Currently, limited information is available on the genomic information of A. veronii strains that cause human gastrointestinal diseases. Here we sequenced, assembled and analysed 25 genomes (one complete genome and 24 draft genomes) of A. veronii strains isolated from patients with gastrointestinal diseases using combine sequencing technologies from Illumina and Oxford Nanopore. We also conducted comparative analysis of genomes of 168 global A. veronii strains isolated from different sources. RESULTS: We found that most of the A. veronii strains isolated from patients with gastrointestinal diseases were closely related to each other, and the remaining were closely related to strains from other sources. Nearly 300 putative virulence factors were identified. Aerolysin, microbial collagenase and multiple hemolysins were present in all strains isolated from patients with gastrointestinal diseases. Type III Secretory System (T3SS) in A. veronii was in AVI-1 genomic island identified in this study, most likely acquired via horizontal transfer from other Aeromonas species. T3SS was significantly less present in A. veronii strains isolated from patients with gastrointestinal diseases as compared to strains isolated from fish and domestic animals. CONCLUSIONS: This study provides novel information on source of infection and virulence of A. veronii in human gastrointestinal diseases.

Fecal microbiome profiles of neonatal dairy calves with varying severities of gastrointestinal disease.

Gastrointestinal disease (GI) is the most common illness in pre-weaned dairy calves. Studies have associated the fecal microbiome composition with health status, but it remains unclear how the microbiome changes across different levels of GI disease and breeds. Our objective was to associate the clinical symptoms of GI disease with the fecal microbiome. Fecal samples were collected from calves (n = 167) of different breeds (Holstein, Jersey, Jersey-cross and beef-cross) from 4-21 d of age. Daily clinical evaluations assessed health status. Calves with loose or watery feces were diagnosed with diarrhea and classified as bright-sick (BS) or depressed-sick (DS) according to behavior. Calves with normal or semiformed feces and no clinical illness were classified as healthy (H). One hundred and three fecal samples were obtained from consistently healthy calves and 64 samples were from calves with diarrhea (n = 39 BS; n = 25 DS). The V3-V4 region of 16S rRNA gene was sequenced and analyzed. Differences were identified by a linear-mixed effects model with a negative binomial error. DS and Jersey calves had a higher relative abundance of Streptococcus gallolyticus relative to H Holstein calves. In addition, DS calves had a lower relative abundance of Bifidobacterium longum and an enrichment of Escherichia coli. Species of the genus Lactobacillus, such as an unclassified Lactobacillus, Lactobacillus reuteri, and Lactobacillus salivarius were enriched in calves with GI disease. Moreover, we created a model to predict GI disease based on the fecal microbiome composition. The presence of Eggerthella lenta, Bifidobacterium longum, and Collinsella aerofaciens were associated with a healthy clinical outcome. Although lactobacilli are often associated with beneficial probiotic properties, the presence of E. coli and Lactobacillus species had the highest coefficients positively associated with GI disease prediction. Our results indicate that there are differences in the fecal microbiome of calves associated with GI disease severity and breed specificities.

Gastrointestinal Dysfunction in Parkinson's Disease.

There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The clinical features of GI dysfunction in PD have been clearly identified and innovative research has demonstrated the presence of pathology within the enteric nervous system (ENS) in individuals with PD, leading to suggestions that the GI system may be ground zero for the genesis and the portal of entry of PD pathology, which then ascends via the vagus nerve to the central nervous system (CNS). This theory, as well as the more recent recognition of the association of PD with dysbiosis within the gut microbiota, has been the object of intense study and scrutiny. Since most PD medications are absorbed through the GI system, the need for better understanding of changes within the GI tract that may potentially affect the pattern of response to medications has become evident. In this review, current knowledge of the pathophysiology of changes within the GI tract and the gut microbiome of individuals with PD, including changes that occur with progression of the disease, will be addressed. We focus on common clinical GI problems in PD that can arise from different segments of the GI tract. Relevant diagnostic evaluations and treatment options for each of these problems will be reviewed.

Intestinal toll-like receptor 4 knockout alters the functional capacity of the gut microbiome following irinotecan treatment.

PURPOSE: Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. Toll-like receptor 4 (TLR4) and the gut microbiome have previously been implicated in gastrointestinal toxicity and diarrhea; however, the link between these two factors has not been definitively determined. We used a tumor-bearing, intestinal epithelial cell (IEC) TLR4 knockout model (Tlr4ΔIEC) to assess microbiome changes following irinotecan treatment. We then determined if a fecal microbiota transplant (FMT) between Tlr4ΔIEC and wild-type (WT) mice altered irinotecan-induced gastrointestinal toxicity. METHODS: MC-38 colorectal cancer cells were injected into WT and Tlr4ΔIEC mice. Fecal samples were collected prior to tumor inoculation, prior to irinotecan treatment and at cull. 16S rRNA gene sequencing was used to assess changes in the microbiome. Next, FMT was used to transfer the microbiome phenotype between Tlr4ΔIEC and WT mice prior to irinotecan treatment. Gastrointestinal toxicity symptoms were assessed. RESULTS: In study 1, there were no compositional differences in the microbiome between Tlr4ΔIEC and WT mice at baseline. However, predicted functional capacity of the microbiome was different between WT and Tlr4ΔIEC at baseline and post-irinotecan. In study 2, Tlr4ΔIEC mice were protected from grade 3 diarrhea. Additionally, WT mice who did not receive FMT had more colonic damage in the colon compared to controls (P = 0.013). This was not seen in Tlr4ΔIEC mice or WT mice who received FMT (P > 0.05). CONCLUSION: Tlr4ΔIEC and WT had no baseline compositional microbiome differences, but functional differences at baseline and following irinotecan. FMT altered some aspects of irinotecan-induced gastrointestinal toxicity.

The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder.

Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.

Zinc is a key regulator of gastrointestinal development, microbiota composition and inflammation with relevance for autism spectrum disorders.

Gastrointestinal (GI) problems and microbiota alterations have been frequently reported in autism spectrum disorders (ASD). In addition, abnormal perinatal trace metal levels have been found in ASD. Accordingly, mice exposed to prenatal zinc deficiency display features of ASD-like behavior. Here, we model GI development using 3D intestinal organoids grown under zinc-restricted conditions. We found significant morphological alterations. Using proteomic approaches, we identified biological processes affected by zinc deficiency that regulate barrier permeability and pro-inflammatory pathways. We confirmed our results in vivo through proteomics studies and investigating GI development in zinc-deficient mice. These show altered GI physiology and pro-inflammatory signaling, resulting in chronic systemic and neuroinflammation, and gut microbiota composition similar to that reported in human ASD cases. Thus, low zinc status during development is sufficient to compromise intestinal barrier integrity and activate pro-inflammatory signaling, resulting in changes in microbiota composition that may aggravate inflammation, altogether mimicking the co-morbidities frequently observed in ASD.