Microbiomic and Metabolomic Analyses Unveil the Protective Effect of Saffron in a Mouse Colitis Model.

Despite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD and how the microbiome and metabolome play a role has not been explored extensively. We aimed to establish whether saffron treatment modulates the host microbiome and metabolic profile in experimental colitis. Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron in a dose of 20 mg/kg body weight or vehicle through daily gavage. On day 10, stool pellets from mice were collected and analyzed to assess saffron's effect on fecal microbiota and metabolites through 16S rRNA sequencing and untargeted primary metabolite analysis. Saffron treatment maintained gut microbiota homeostasis by counter-selecting pro-inflammatory bacteria and maintained Firmicutes/Bacteroides ratio, which was otherwise disturbed by DSS treatment. Several metabolites (uric acid, cholesterol, 2 hydroxyglutaric acid, allantoic acid, 2 hydroxyhexanoic acid) were altered significantly with saffron treatment in DSS-treated mice, and this might play a role in mediating saffron's colitis-mitigating effects. These data demonstrate saffron's therapeutic potential, and its protective role is modulated by gut microbiota, potentially acting through changes in metabolites.

Fe(III)-Anchored Porphyrin-Based Nanoporous Covalent Organic Frameworks for Green Synthesis of Cyclic Carbonates from Olefins and CO2 under Atmospheric Pressure Conditions.

The utilization of carbon dioxide (CO2) as a C1 source coupled with olefins, readily accessible feedstocks, offers dual advantages of mitigating atmospheric carbon dioxide and green synthesis of valuable chemicals. In this regard, herein we demonstrate the application of Fe(III)-anchored porphyrin-based covalent organic framework (P-COF) as a promising recyclable catalyst for one-step generation of cyclic carbonates (CCs), value-added commodity chemicals from olefins and CO2, under mild atmospheric pressure conditions. Moreover, this one-pot synthesis was applied to transform various olefins (aliphatic and aromatic) into the corresponding CCs in good yield and selectivity. In addition, the Fe(III)@P-COF showed good recyclability and durability for multiple reuse cycles without losing its catalytic activity. Notably, this one-step synthesis strategy presents an eco-friendly, atom-economic alternative to the conventional two-step process requiring epoxides. This work represents a rare demonstration of porphyrin COF-catalyzed one-pot CC synthesis by utilizing readily available olefins at atmospheric pressure of carbon dioxide.

Novel Circulating and Tissue Monocytes as Well as Macrophages in Pancreatitis and Recovery.

BACKGROUND AND AIMS: Acute pancreatitis (AP) is an inflammatory disease with mild to severe course that is associated with local and systemic complications and significant mortality. Uncovering inflammatory pathways that lead to progression and recovery will inform ways to monitor and/or develop effective therapies. METHODS: We performed single-cell mass Cytometry by Time Of Flight (CyTOF) analysis to identify pancreatic and systemic inflammatory signals during mild AP (referred to as AP), severe AP (SAP), and recovery using 2 independent experimental models and blood from patients with AP and recurrent AP. Flow cytometric validation of monocytes subsets identified using CyTOF analysis was performed independently. RESULTS: Ly6C+ inflammatory monocytes were the most altered cells in the pancreas during experimental AP, recovery, and SAP. Deep profiling uncovered heterogeneity among pancreatic and blood monocytes and identified 7 novel subsets during AP and recovery, and 6 monocyte subsets during SAP. Notably, a dynamic shift in pancreatic CD206+ macrophage population was observed during AP and recovery. Deeper profiling of the CD206+ macrophage identified 7 novel subsets during AP, recovery, and SAP. Differential expression analysis of these novel monocyte and CD206+ macrophage subsets revealed significantly altered surface (CD44, CD54, CD115, CD140a, CD196, podoplanin) and functional markers (interferon-γ, interleukin 4, interleukin 22, latency associated peptide-transforming growth factor-ß, tumor necrosis factor-α, T-bet, RoRγt) that were associated with recovery and SAP. Moreover, a targeted functional analysis further revealed distinct expression of pro- and anti-inflammatory cytokines by pancreatic CD206+ macrophage subsets as the disease either progressed or resolved. Similarly, we identified heterogeneity among circulating classical inflammatory monocytes (CD14+CD16-) and novel subsets in patients with AP and recurrent AP. CONCLUSIONS: We identified several novel monocyte/macrophage subsets with unique phenotype and functional characteristics that are associated with AP, recovery, and SAP. Our findings highlight differential innate immune responses during AP progression and recovery that can be leveraged for future disease monitoring and targeting.

Protective Effect of Saffron in Mouse Colitis Models Through Immune Modulation.

BACKGROUND: People with inflammatory bowel disease (IBD) including ulcerative colitis are at risk for colorectal cancer. Despite available effective drugs used to treat IBD, many patients fail or lose response over time with some displaying drug-induced adverse events. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD has not been explored extensively. AIM: To establish whether saffron treatment alleviates inflammation in experimental colitis. METHODS: Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron doses (7.5, 15, 20, 25 mg/kg body weight) or vehicle through daily gavage. On day 11, mice were euthanized and analyzed for gross and microscopic inflammation. Distal colon segments were collected for mRNA and protein expression of HO-1 protein and GPX2, (the downstream targets of NRF-2). Nrf-2 translocation from cytosol to nucleus was confirmed by immunofluorescence, and further Nrf-2 protein expression in nuclear and cytosolic fraction of colon was analyzed by immunoblot. Immune cells were isolated from the lamina propria of mouse colon for flow cytometry-based immunophenotyping. Colitis was also induced in C57BL/6 Ahr knockout and wild type mice to explore the involvement of Ahr-dependent pathways in saffron's protective effect(s). The therapeutic effect of saffron was further validated in another TNBS model of colitis. RESULTS: Saffron 20 mg/kg body weight showed improved colon gross and histology features and led to better body weight, colon length, histology score, and reduced disease activity index (DAI). Saffron significantly decreased pro-inflammatory macrophages (M1), while increasing anti-inflammatory macrophages (M2) and IL10 + dendritic cells. Saffron treatment also enhanced CD3 + T and CD3 + CD8 + T cells followed by increase in different CD3 + CD4 + T cells subsets like CD25 + T cells, FoxP3 + CD25 + regulatory T cells, and CD4 + FOXP3 + CD25-regulatory T cells. Immunoblot analysis showed a significant increase in HO-1/GPX2 protein expression. With saffron treatment, Nrf-2 translocation into nucleus from cytosol also supports the involvement of Nrf-2 and its downstream targets in the protective effect of saffron. Further, we demonstrated that saffron in part exert anti-inflammatory effect through activation of aryl hydrocarbon receptor (AhR)-nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways. CONCLUSION: These data demonstrate saffron's therapeutic potential and its protective role in part via Ahr/Nrf-2 pathways and regulatory innate and adaptive immune cells.

Saffron Pre-Treatment Promotes Reduction in Tissue Inflammatory Profiles and Alters Microbiome Composition in Experimental Colitis Mice.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with an incompletely understood pathogenesis. Long-standing colitis is associated with increased risk of colon cancer. Despite the availability of various anti-inflammatory and immunomodulatory drugs, many patients fail to respond to pharmacologic therapy and some experience drug-induced adverse events. Dietary supplements, particularly saffron (Crocus sativus), have recently gained an appreciable attention in alleviating some symptoms of digestive diseases. In our study, we investigated whether saffron may have a prophylactic effect in a murine colitis model. Saffron pre-treatment improved the gross and histopathological characteristics of the colonic mucosa in murine experimental colitis. Treatment with saffron showed a significant amelioration of colitis when compared to the vehicle-treated mice group. Saffron treatment significantly decreased secretion of serotonin and pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, in the colon tissues by suppressing the nuclear translocation of NF-κB. The gut microbiome analysis revealed distinct clusters in the saffron-treated and untreated mice in dextran sulfate sodium (DSS)-induced colitis by visualization of the Bray-Curtis diversity by principal coordinates analysis (PCoA). Furthermore, we observed that, at the operational taxonomic unit (OTU) level, Cyanobacteria were depleted, while short-chain fatty acids (SCFAs), such as isobutyric acid, acetic acid, and propionic acid, were increased in saffron-treated mice. Our data suggest that pre-treatment with saffron inhibits DSS-induced pro-inflammatory cytokine secretion, modulates gut microbiota composition, prevents the depletion of SCFAs, and reduces the susceptibility to colitis.

Identification, antibiotic resistance, and virulence profiling of Aeromonas and Pseudomonas species from wastewater and surface water.

Aquatic environments are hotspots for the spread of antibiotic-resistant bacteria and genes due to pollution caused mainly by anthropogenic activities. The aim of this study was to evaluate the impact of wastewater effluents, informal settlements, hospital, and veterinary clinic discharges on the occurrence, antibiotic resistance profile and virulence signatures of Aeromonas spp. and Pseudomonas spp. isolated from surface water and wastewater. High counts of Aeromonas spp. (2.5 (± 0.8) - 3.3 (± 0.4) log10 CFU mL-1) and Pseudomonas spp. (0.6 (± 1.0) - 1.8 (± 1.0) log10 CFU mL-1) were obtained. Polymerase chain reaction (PCR) and MALDI-TOF characterization identified four species of Aeromonas and five of Pseudomonas. The isolates displayed resistance to 3 or more antibiotics (71% of Aeromonas and 94% of Pseudomonas). Aeromonas spp. showed significant association with the antibiotic meropenem (χ2 = 3.993, P < 0.05). The virulence gene aer in Aeromonas was found to be positively associated with the antibiotic resistance gene blaOXA (χ2 = 6.657, P < 0.05) and the antibiotic ceftazidime (χ2 = 7.537, P < 0.05). Aeromonas recovered from both wastewater and surface water displayed high resistance to ampicillin and had higher multiple antibiotic resistance (MAR) indices close to the hospital. Pseudomonas isolates on the other hand exhibited low resistance to carbapenems but very high resistance to the third-generation cephalosporins and cefixime. The results showed that some of the Pseudomonas spp. and Aeromonas spp. isolates were extended-spectrum ß-lactamase producing bacteria. In conclusion, the strong association between virulence genes and antibiotic resistance in the isolates shows the potential health risk to communities through direct and indirect exposure to the water.

Safety & efficacy of an intravasal, one-time injectable & non-hormonal male contraceptive (RISUG): A clinical experience.

Background & objectives: For improved male contraception, a new polymeric drug molecule - Reversible Inhibition of Sperm under Guidance (RISUG) has been synthesized and has been found to be effective, safe and reversible in various animal species. Phase-I and phase-II clinical trials have confirmed its safety and contraceptive efficacy. The present study was undertaken as a multicentric-limited phase-III clinical trial to test the efficacy and safety of RISUG in human volunteers. Methods: One hundred and thirty nine young males each having at least two children and living with wife were given 120 µl of RISUG as bilateral vas intraluminal injection. After the single-dose administration, the individuals were followed in respect of general health and semen parameters. Their wives were also followed particularly to determine onset of pregnancy. Results: During the six month follow up, the health of male volunteers and their wives was normal with no significant adverse effects. Temporary scrotal enlargement and mild scrotal and inguinal region pain were manifested in most individuals and resolved within one month without any routine activity impairment. In six individuals, there was injection procedure failure and azoospermia was not achieved. The other 133 individuals had either severe oligozoospermia or azoospermia at the first semen examination one month following RISUG injection; 82.7 per cent individuals had continued azoospermia in the month following first semen examination onwards and the rest 17.3 per cent manifested azoospermia within three to six months. Interpretation & conclusions: RISUG intravasal injection appears to be a safe clinical procedure with no significant adverse effects and has high sustained contraceptive efficacy. The localized intervention and continued contraceptive action on single-dose administration were significant features of the RISUG technology.

Comparison of droplet digital PCR and quantitative PCR for the detection of Salmonella and its application for river sediments.

Despite advances in microbial detection that quantitative polymerase chain reaction (qPCR) has led to, complex environmental samples, such as sediments, remain a challenge due to presence of PCR inhibitors. Aquatic sediments accumulate particle-bound microbial contaminants and thereby reflect a cumulative microbial load over time. The relatively new droplet digital PCR (ddPCR) has emerged as a direct quantitative method, highly tolerant to PCR inhibitors and relinquishing the necessity for calibration/standard curves. Information is virtually absent where ddPCR has been applied to detect pathogenic organisms in aquatic sediments. This study compared the efficacy of ddPCR with qPCR, for quantification of Salmonella in sediments from the Palmiet River near an informal settlement in Durban, South Africa. ddPCR significantly improved both analytical sensitivity and detection of low concentrations of Salmonella as compared to qPCR. The expected copy numbers measured from both qPCR and ddPCR showed good R2 values (0.999 and 0.994, respectively). The site mostly affected by the informal settlements exhibited Salmonella in the range of 255 ± 37 and 818 ± 30 Salmonella/g (p ≤ 0.0001) in qPCR and ddPCR, respectively. The improved detection of Salmonella in sediments with ddPCR makes it a promising technical method for the quantification of Salmonella in multifarious environmental samples.

Antibiotic Resistant Superbugs: Assessment of the Interrelationship of Occurrence in Clinical Settings and Environmental Niches.

The increasing threat to global health posed by antibiotic resistance remains of serious concern. Human health remains at higher risk due to several reported therapeutic failures to many life threatening drug resistant microbial infections. The resultant effects have been prolonged hospital stay, higher cost of alternative therapy, increased mortality, etc. This opinionated review considers the two main concerns in integrated human health risk assessment (i.e., residual antibiotics and antibiotic resistant genes) in various compartments of human environment, as well as clinical dynamics associated with the development and transfer of antibiotic resistance (AR). Contributions of quorum sensing, biofilms, enzyme production, and small colony variants in bacteria, among other factors in soil, water, animal farm and clinical settings were also considered. Every potential factor in environmental and clinical settings that brings about AR needs to be identified for the summative effects in overall resistance. There is a need to embrace coordinated multi-locational approaches and interrelationships to track the emergence of resistance in different niches in soil and water versus the hospital environment. The further integration with advocacy, legislation, enforcement, technological innovations and further research input and recourse to WHO guidelines on antibiotic policy would be advantageous towards addressing the emergence of antibiotic resistant superbugs.

Asymmetric Extraction: How to Use Smartly.

This case report summarizes the use of asymmetric extraction to smartly relieve crowding without increasing the total treatment time, with the added advantage of not using any complicated mechanics.

Correction of a Overjet and Overbite In Class II Division 1 Malocclusion Using Twin Block Appliance Therapy: A Case Report.

Class II division 1 malocclusion is the most common malocclusion. It shows specific clinical characteristics such as large overiet and deep overbite resulting in a soft tissue profile imbalance. Majority of the patients with class II division 1 malocclusions have an underlying skeletal discrepancy between the maxilla and mandible. The treatment of skeletal class II division 1 malocclusion is done taking into consideration the age, growth potential, severity of malocclusion, and compliance of patient with treatment. Myofunctional appliances can be successfully used to treat growing patients with class II division 1 malocclusion. This article presents a discussion on successful treatment of class II division 1 malocclusion with growth modification approach using twin block appliances.

Two-port mini laparoscopic cholecystectomy compared to standard four-port laparoscopic cholecystectomy.

INTRODUCTION: Two-port mini laparoscopic cholecystectomy (LC) has been proposed as a safe and feasible technique. However, there are limited studies to evaluate the effectiveness of the procedure. This study is a prospective randomised trial to compare the standard four-port LC with two-port mini LC. MATERIALS AND METHODS: A total of 116 consecutive patients undergoing LC were randomised to four-port/two-port mini LC. In two-port mini LC, a 10-mm umbilical and a 5-mm epigastric port were used. Outcomes measured were duration and difficulty of operation, post-operative pain, analgesia requirements, post-operative stay, complications and cosmetic score at 30 days. RESULTS: Out of 116 patients, the ratio of M:F was 11:92, with mean age 40.79 ± 12.6 years. Twelve patients (nine in four-port group and three in two-port group) were lost to follow-up. The mean operative time were similar (P = 0.727). Post-operative pain was significantly low in the two-port group at up to 24 hrs (P = 0.023). The overall analgesia requirements (P = 0.003) and return to daily activity (P = 0.00) were significantly lower in two-port group. The cosmesis score of the two-port group was better than four-port group (P = 0.00). However, the length of hospital stay (P = 0.760) and complications (P = 0.247) were similar between the two groups. CONCLUSION: Two-port mini LC resulted in reduced pain, need for analgesia, and improved cosmesis without increasing the operative time and complication rates compared to that in four-port LC. Thus, it can be recommended in selected patients.

Direct C-H alkylation of 3,4-dihydroquinoxaline-2-ones with N-(acyloxy)phthalimides via radical-radical cross coupling.

We present an organophotoredox-catalyzed direct Csp3-H alkylation of 3,4-dihydroquinoxalin-2-ones employing N-(acyloxy)pthalimides to provide corresponding products in good yields. A broad spectrum of NHPI esters (1°, 2°, 3°, and sterically encumbered) participates in the photoinduced alkylation of a variety of 3,4-dihydroquinoxalin-2-ones. In general, mild conditions, broad scope with good functional group tolerance, and scalability are the salient features of this direct alkylation process.

Pyrene-Based Nanoporous Covalent Organic Framework for Carboxylation of C-H Bonds with CO2 and Value-Added 2-Oxazolidinones Synthesis under Ambient Conditions.

The selective carbon capture and utilization (CCU) as a one-carbon (C1) feedstock offers dual advantages for mitigating the rising atmospheric CO2 content and producing fine chemicals/fuels. In this context, herein, we report the application of a porous bipyridine-functionalized, pyrene-based covalent organic framework (Pybpy-COF) for the stable anchoring of catalytic Ag(0) nanoparticles (NPs) and its catalytic investigation for fixation of CO2 to commodity chemicals at ambient conditions. Notably, Ag@Pybpy-COF showed excellent catalytic activity for the carboxylation of various terminal alkynes to corresponding alkynyl carboxylic acids/phenylpropiolic acids via C-H bond activation under atmospheric pressure conditions. Besides, carboxylative cyclization of various propargylic amines with CO2 to generate 2-oxazolidinones, an important class of antibiotics, has also been achieved under mild conditions. This significant catalytic activity of Ag@Pybpy-COF with wide functional group tolerance is rendered by the presence of highly exposed, alkynophilic Ag(0) catalytic sites decorated on the pore walls of high surface area (787 m2 g-1) Pybpy-COF. Further, density functional theory calculations unveiled the detailed mechanistic path of the Ag@Pybpy-COF-catalyzed transformation of CO2 to alkynyl carboxylic acids and 2-oxazolidinones. Moreover, the catalyst showed high recyclability for several cycles of reuse without significant loss in its catalytic activity and structural rigidity. This work demonstrates the promising application of Pybpy-COF for stable anchoring of Ag NPs for successful transformation of CO2 to valuable commodity chemicals at ambient conditions.

Determination of viable Salmonellae from potable and source water through PMA assisted qPCR.

Resource constrained countries identified as endemic zones for pathogenicity of Salmonella bear an economic burden due to recurring expenditure on medical treatment. qPCR used for Salmonella detection could not discriminate between viable and nonviable cells. Propidium monoazide (PMA) that selectively penetrates nonviable cells to cross-link their DNA, was coupled with ttr gene specific qPCR for quantifying viable salmonellae in source/potable waters collected from a north Indian city. Source water (raw water for urban potable water supply) and urban potable water exhibited viable salmonellae in the range of 2.1×10(4)-2.6×10(6) and 2-7160CFU/100mL, respectively. Potable water at water works exhibited DNA from dead cells but no viable cells were detected. PMA assisted qPCR could specifically detect low numbers of live salmonellae in Source and potable waters. This strategy can be used in surveillance of urban potable water distribution networks to map contamination points for better microbial risk management.

Modified protrusion arch for anterior crossbite correction - a case report.

Borderline and mild skeletal Class III relationships in adult patients are usually treated by orthodontic camouflage. Reasonably rood results have been achieved with nonsurgical teatment of anterior crossbite. Class III malocclusion may be associated with mandibular prognathism, maxillary retrognathism, or both. Class III maxillary retrognathism generally involves anterior crossbite, which must be opened if upper labial brackets are to be bonded. If multiple teeth are in crossbite, after opening the bite usual step is to ligate forward or advancement arch made of 0.018" or 0.020" stainless steel or NiTi wire main arch that must be kept separated 2 mm from the slot ofupper incisor braces. Two stops or omegas are made 1 mm mesial to the tubes of the molar bands that will impede main arch from slipping,and in this manner the arch will push the anterior teeth forward Here we have fabricated a modified multiple loop protrusion arch to correct an anterior crossbite with severe crowding that was not amenable to correct by advancement arches.

An interim bite raiser.

Patients with deep bites or crossbites often need temporary bite opening to prevent mandibular brackets from being sheared off and to allow unobstructed tooth movement. Here we present a simple auxiliary occlusal extension for temporary bite opening to correct an anterior crossbite. The bite plane is hygienic, less intrusive to the tongue space and prevents supra-eruption of the adjacent as well as opposing teeth.

Bio-capture of S. Typhimurium from surface water by aptamer for culture-free quantification.

In this study, a DNA aptamer was used to bio-capture Salmonella enterica serovar Typhimurium from surface water collected from highly endemic zone prior to culture-free detection through Molecular-Beacon based real-time PCR assay targeting invA gene. The assay could detect S. Typhimurium cells (1 CFU/PCR or 100 CFU/ml) selectively captured by serovar specific DNA aptamer. The observations indicate that all the water samples (n=40) collected from the river Gomti were contaminated by S. Typhimurium (31400-1 × 10(7) CFU/100 ml). The pre-analytical step in the form of serovar specific DNA aptamer based bio-capture of the bacterial cell was found to enhance the sensitivity of the florescent probe based real-time PCR assay during detection of S. Typhimurium in environmental samples exhibiting natural PCR inhibitors and high background bacterial flora. The assay could be used for the regular monitoring of surface waters for forecasting and management of non-typhoidal Salmonellosis in south Asia.

The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial.

BACKGROUND & AIMS: Probiotics contain living microorganisms consumed for their putative benefits on the intestinal microbiota and general health and a concept is emerging to use probiotic as a therapeutic intervention to reduce proton pump inhibitors (PPIs) negative effects, but data is lacking. The use of PPIs can result in disordered gut microbiota, leading to a risk of enteric infections. PPIs are frequently prescribed in the general practice setting for gastroesophageal reflux disease (GERD), peptic ulcer disease, and related conditions. Despite the availability and widespread use of probiotics and acid-suppressing medications, the effect of PPIs-induced gastric acid suppression on the survival and colonization of probiotics bacterial species is currently unclear. We hypothesized that gastric acid suppression may improve intestinal colonization of probiotics bacterial species and probiotic intervention may have a potential role in mitigating untoward effects of PPI. METHODS: In a randomized, double-blind, placebo-controlled study, healthy subjects were given either proton pump inhibitor (PPI, n = 15) or placebo (n = 15) over 6 weeks. All subjects then consumed multi-strain probiotics from weeks 2-6. Thirty participants (10 males, 20 females, age range: 18-56 years) were enrolled in the study. Shotgun metagenomic sequencing and untargeted metabolomics analyses were performed on stool samples collected at week 0, 2, and 6. RESULTS: Short term PPI treatment increased the microbial abundance of Streptococcaceae (p = 0.004), Leuconostacaceae (p = 0.001), and Pasteurellaceae (p = 0.020) at family level and corresponding genus levels. The metabolomic analysis of the stools revealed a change in 10 metabolites where Gly Arg Val and phenylacetic acid were consistently increased compared to the baseline. Probiotic intervention inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p = 0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. Notably, PPI enhanced the colonization of certain probiotic bacterial species like Streptococcus thermophilus (p < 0.05) along with other species present in the multi-strain probiotic. CONCLUSION: Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations. CLINICAL TRIALS. GOV, NUMBER: NCT03327051.