Alex Rodriguez-Palacios

Case Western Reserve University School of Medicine · Gastroenterology & Liver Diseases - Dept. of Medicine; Digestive Diseases Research Institute

Understanding the complex link between inflammation, gut health, and dietary amino acids is becoming increasingly important in the pathophysiology of inflammatory bowel disease (IBD). This study tested the hypothesis that a leucine-rich diet could attenuate inflammation and improve gut health in a mouse model of IBD. Specifically, we investigated t...

Background/Objectives: Dietary fats have been linked to the increasing incidence of chronic diseases, including inflammatory bowel diseases (IBD), namely, Crohn’s disease (CD). Methods: This study investigated the impact of pentadecanoic acid (C15:0), a type of an odd-numbered chain saturated fatty acid, for its potential anti-inflammatory properti...

Walnuts (Juglans regia L.) have shown promising effects in terms of ameliorating inflammatory bowel disease (IBD), attributed to their abundant bioactive compounds. This review comprehensively illustrates the key mechanisms underlying the therapeutic potential of walnuts in IBD management, including the modulation of intestinal mucosa permeability,...

Backgrounds & Aims Bile acids (BAs) are core gastrointestinal metabolites with dual functions in lipid absorption and cell signaling. BAs circulate between the liver and distal small intestine (i.e., ileum), yet the dynamics through which complex BA pools are absorbed in the ileum and interact with host intestinal cells in vivo remain poorly unders...

Comensal Bacteroidota (Bacteroidota) and Enterobacteriacea are often linked to gut inflammation. However, the causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism in Bacteroidota remain unclear. By using the classical lipopolysaccharide/O-antigen ‘rfb operon’ in Enterobacteriaceae as a surface...

In medicine, parasitic cysts (e.g., brain cysticerci) are believed to be sterile, and are primarily treated with antiparasitic medications, not antibiotics, which could prevent abscess formation and localized inflammation. This study quantified the microbial composition of parasitic cysts in a wild rodent, using multi-kingdom metagenomics to compre...

In medicine, parasitic cysts or cysticerci (fluid-filled cysts, larval stage of tapeworms) are believed to be sterile (no bacteria), and therein, the treatment of cysticerci infestations of deep extra-intestinal tissues ( e . g ., brain) relies almost exclusively on the use of antiparasitic medications, and rarely antibiotics. To date, however, it...

Surgically removed bowels from Crohn's disease patients exhibit a novel form of micropathologies known as cavernous fistulous tract microlesions (CavFT), resembling fissures. We announce the genomes/plasmids and antimicrobial resistance genes of six CavFT bacterial isolates representing the Bacteroidota genera Bacteroides and Phocaeicola. Plasmids...

Crohn’s disease (CD) has been traditionally viewed as a chronic inflammatory disease that cause gut wall thickening and complications, including fistulas, by mechanisms not understood. By focusing on Parabacteroides distasonis (presumed modern succinate-producing commensal probiotic), recovered from intestinal microfistulous tracts (cavernous fistu...

The causes for variability of pro-inflammatory surface antigens that affect gut commensal/opportunistic dualism within the phylum Bacteroidota remain unclear (1, 2). Using the classical lipopolysaccharide/O-antigen ‘ rfb operon’ in Enterobacteriaceae as a surface antigen model (5-gene-cluster rfbABCDX ), and a recent rfbA- typing strategy for strai...

Background While artificial sweeteners are deemed safe, preclinical studies indicate that artificial sweeteners contribute to gastrointestinal inflammation. Little is known about patients’ perceptions and consumption of artificial sweeteners in inflammatory bowel disease (IBD). We surveyed the consumption frequency and beliefs of IBD patients and c...

Purpose Maltodextrin (MDX) is a polysaccharide food additive commonly used as oral placebo/control to investigate treatments/interventions in humans. The aims of this study were to appraise the MDX effects on human physiology/gut microbiota, and to assess the validity of MDX as a placebo-control. Methods We performed a systematic review of randomi...

Parabacteroides distasonis (Pdis) is the type species for the new Parabacteroides genus, and a gut commensal of the Bacteroidetes phylum. Emerging reports (primarily based on reference strain/ATCC-8503) concerningly propose that long-known opportunistic pathogen Pdis is a probiotic. We posit there is an urgent need to characterize the pathogenicity...

During a pandemic, there are multiple concurrent clinical and scientific priorities, including the need to understand the pathophysiology of the disease, the different modes of transmission, how patient care can be optimized, as well as the need to developmathematicalmodels that can now cast and forecast the progression of infections within given p...

Reactive oxygen species play a major role in the induction of programmed cell death and numerous diseases. Production of reactive oxygen species is ubiquitous in biological systems such as humans, bacteria, fungi/yeasts, and plants. Although reactive oxygen species are known to cause diseases, little is known about the importance of the combined ox...

Since the introduction of artificial sweeteners (AS) to the North American market in the 1950s, a growing number of epidemiological and animal studies have suggested that AS may induce changes in gut bacteria and gut wall immune reactivity, which could negatively affect individuals with or susceptible to chronic inflammatory conditions such as infl...

Human coronaviruses present a substantial global disease burden, causing damage to populations’ health, economy, and social well-being. Glycans are one of the main structural components of all microbes and organismic structures, including viruses—playing multiple essential roles in virus infection and immunity. Studying and understanding virus glyc...

Bile acids are lipid-emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, bile acids can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain bile acid homeostasis in hepatocytes and enterocytes3, but it is...

Germ-free (GF) animals and the housing systems necessary to maintain animals as GF during breeding, or as “gnotobiotic” (GN) during specifically designed experiments, have been based on a traditional electrically pressurized ventilation system that influx HEPA-filtered air into the housing units that have existed since at least the 1940s. Since the...

Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random...

With the epidemic of human obesity, dietary fats have increasingly become a focal point of biomedical research. Epidemiological studies indicate that high-fat diets (HFDs), especially those rich in long-chain saturated fatty acids (e.g., Western Diet, National Health Examination survey; NHANES ‘What We Eat in America’ report) have multi-organ pro-i...

Background The current nutritional composition of the “American diet” (AD; also known as Western diet) has been linked to the increasing incidence of chronic diseases, including inflammatory bowel disease (IBD), namely Crohn disease (CD). Objectives This study investigated which of the 3 major macronutrients (protein, fat, carbohydrates) in the AD...

Innate lymphoid cells (ILCs) are enriched at barrier surfaces, including the gastrointestinal tract. While most studies have focused on the balance between pathogenic group 1 ILCs (ILC1s) and protective ILC3s in maintaining gut homeostasis and during chronic intestinal inflammation, such as Crohn's disease (CD), less is known regarding ILC2s. Using...

Parabacteroides distasonis is the type strain for the genus Parabacteroides, a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in the 1930s from a clinical specimen as Bacteroides distasonis, the strain was re-classified to form the new genus Parabacteroides in 2006. Cu...

We present an opinion that the widespread understanding of facemask effectiveness and public droplet safety is needed to sustainably control COVID-19 transmission in public settings. Contradictory messages from both mass media and some political leaders have resulted in the reversal of facemask mandates and public distrust of advice. To recover pub...

Several studies have measured the effectiveness of masks at retaining particles of various sizes in vitro. To identify a functional in vivo model, herein we used germ-free (GF) mice to test the effectiveness of textiles as filtration material and droplet barriers to complement available in vitro-based knowledge. Herein, we report a study conducted...

Alistipes is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the Bacteroidetes phylum, which are highly relevant in dysbiosis and disease. According to the taxonomy database at The National Center for Biotechnology Information, the genus consists of 13 sp...

The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy” donor is transplanted into a person with illness, has been...

The main form of COVID-19 transmission is via “oral-respiratory droplet contamination” (droplet: very small drop of liquid) produced when individuals talk, sneeze, or cough. In hospitals, health-care workers wear facemasks as a minimum medical “droplet precaution” to protect themselves. Due to the shortage of masks during the pandemic, priority is...

The main form of COVID-19 transmission is via oral-respiratory droplet contamination (droplet; very small drop of liquid) produced when individuals talk, sneeze or cough. In hospitals, health-care workers wear facemasks as a minimum medical droplet precaution to protect themselves. Due to the shortage of masks during the pandemic, priority is given...

Due to the shortage of masks during the pandemic, we recently demonstrated that household textiles are effective environmental droplet barriers (EDBs) with identical droplet retention potential as medical masks. To further promote the implementation of a universal community droplet reduction solution based on a synchronized encouragement/enforcemen...

Background: Multimodal diseases are those in which affected individuals can be divided into subtypes (or ‘data modes’); for instance, ‘mild’ vs. ‘severe’, based on (unknown) modifiers of disease severity exemplified in the majority of microbiome-mediated human diseases. Studies have shown that despite the inclusion of a large number of subjects, th...

Multimodal diseases are those in which affected individuals can be divided into subtypes (or ‘data modes’); for instance, ‘mild’ vs. ‘severe’, based on (unknown) modifiers of disease severity. Studies have shown that despite the inclusion of a large number of subjects, the causal role of the microbiome in human diseases remains uncertain. The role...

With >70,000 yearly publications using mouse data, mouse models represent the best engrained research system to address numerous biological questions across all fields of science. Concerns of poor study and microbiome reproducibility also abound in the literature. Despite the well-known, negative-effects of data clustering on interpretation and stu...

Clostridioides difficile (CD) is a spore-forming bacterium that causes life-threatening intestinal infections in humans. Although formerly regarded as exclusively nosocomial, there is increasing genomic evidence that person-to-person transmission accounts for only <25% of cases, supporting the culture-based hypothesis that foods may be routine sour...

Background Inflammatory Bowel Disease (IBD) results from an imbalanced immune response toward the gut microbiota. Disruptions in the gut microbiota are proposed as critical elements that could foster pro-inflammatory imbalances and cause active flares IBD. Diet has been shown to have a pro-inflammatory effect in Crohn’s disease (CD) but not much is...

Significance Here we demonstrate that IL-1α neutralization reduces the severity of disease in a mouse model of Crohn’s disease. Unexpectedly, IL-1α neutralization exerts its antiinflammatory effects by modulating the gut microbial ecosystem, and corrected the mucosal dysbiosis. Although studies report that the gut microbiome affects cytokine produc...

Clostridioides difficile (CD) is a spore-forming bacterium that causes life-threatening intestinal infections in humans. Although formerly regarded as exclusively nosocomial, there is increasing genomic evidence that person-to-person transmission accounts for only <25% of cases, supporting the culture-based hypothesis that foods may be routine sour...

Background Inflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD. Meth...

The negative effects of data clustering due to (intra-class/spatial) correlations are well-known in statistics to interfere with interpretation and study power. Therefore, it is unclear why housing many laboratory mice (>4), instead of one-or-two per cage, with the improper use/reporting of clustered-data statistics, abound in the literature. Among...

Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) of the digestive tract in humans. There is evidence that Parabacteroides distasonis could contribute to IBD. Here, we present the complete genome sequence of a strain designated CavFT-hAR46, which was isolated from a gut intramural cavernous fistulous tract (CavFT) microlesion in a...

Impact statement: Institutional protocols designed for the oral administration of live microbial communities, either complex or microscopic (microcosmic), to mice do not exist. However, this approach is increasingly employed by investigators focusing on the gut microbiome in experimental research. Herein, we propose two analytically Kappa-based co...

Background Despite great advancements in therapy, it remains unclear why inflammation in the digestive system of patients suffering Crohn’s Disease (CD) is progressive and leads to complications (e.g., enteric fistulas) that are only alleviated by surgical removal of the damaged bowel. By using a three-dimensional profiling method, we recently disc...

Background We have previously shown that neutralization of IL-1α with a specific murine monoclonal antibody (FLO1) in 25-wk old SAMP1/YitFc (SAMP) mice with established CD-like ileitis, ameliorates ileitis severity. These results were associated with gut microbiome alterations. However, whether these effects are a consequence of decreased intestina...

Background The majority of fecal microbiota transplantation (FMT) peer-review publications suggest that 28 days is sufficient to assess the effect of human microbes because studies in healthy mice (C57BL/6J) indicate that transplanted human gut microbiome is ‘stable’. On the contrary, we present data that illustrates that microbiome stability is a...

Background TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain-receptor-3 (DR3), are multifunctional mediators of effector and regulatory immunity. We aimed to evaluate the functional role and therapeutic potential of TL1A/DR3 signaling in Crohn’s disease–like ileitis. Methods Ileitis-prone SAMP1/YitFc (SAMP) and TNFΔARE/+ mice w...

Clostridioides ( Clostridium ) difficile is a spore-forming anaerobic bacterium that causes severe intestinal diseases in humans. Here, we report the complete genome sequence of the first C. difficile foodborne type strain (PCR ribotype 078) isolated from food animals in Canada in 2004, which has 100% similarity to the genome sequence of the histor...

Negative energy balance is a prevalent feature of cystic fibrosis (CF). Pancreatic insufficiency, elevated energy expenditure, lung disease, and malnutrition, all characteristic of CF, contribute to the negative energy balance causing low bodily growth phenotype. As low body weight and BMI strongly correlate with poor lung health and survival of CF...

Background Epidemiological studies indicate that the use of artificial sweeteners doubles the risk for Crohn’s disease (CD). Herein, we experimentally quantified the impact of 6-week supplementation with a commercial sweetener (Splenda; ingredients sucralose maltodextrin, 1:99, w/w) on both the severity of CD-like ileitis and the intestinal microbi...

Germ-Free (GF) research has required highly technical pressurized HEPA-ventilation anchored systems for decades. Herein, we validated a GF system that can be easily implemented and portable using Nested Isolation (NesTiso). GF-standards can be achieved housing mice in non-HEPA-static cages, which only need to be nested 'one-cage-inside-another' res...

Background We recently described cobblestone (Cob) lesions in the ileum of SAMP1/YitFc (SAMP) mice, which is the only inbred mouse strain with polygenic predisposition to Crohn’s disease(CD)-like ileitis. Herein, we quantified the mRNA gene expression differences across microscopically dissected samples from ileal tissues of adult germ-free (GF)-SA...

Background We performed a series of fecal microbiota transplantation (FMT) experiments to determine the functional persistence of human microbiota in our gnotobiotic (hGB) SAMP1/YitFc (SAMP) mouse model of Crohn’s disease (CD)-like ileitis. Methods Groups of sex-matched, 7-wk-old SAMP mice (i.e. before ileitis onset), were inoculated with 200μl (1...