Dental Stem Cells and Lipopolysaccharides: A Concise Review.

Dental tissue stem cells (DTSCs) are well known for their multipotent capacity and regenerative potential. They also play an important role in the immune response of inflammatory processes derived from caries lesions, periodontitis, and gingivitis. These oral diseases are triggered by toxins known as lipopolysaccharides (LPS) produced by gram-negative bacteria. LPS present molecular patterns associated with pathogens and are recognized by Toll-like receptors (TLRs) in dental stem cells. In this review, we describe the effect of LPS on the biological behavior of DTSCs. We also focus on the molecular sensors, signaling pathways, and emerging players participating in the interaction of DTSCs with lipopolysaccharides. Although the scientific advances generated provide an understanding of the immunomodulatory potential of DTSCs, there are still new reflections to explore with regard to their clinical application in the treatment of oral inflammatory diseases.

Pericytes modulate endothelial inflammatory response during bacterial infection.

Pericytes are located around blood vessels, in close contact with endothelial cells. We discovered that pericytes dampen pro-inflammatory endothelial cell responses. Endothelial cells co-cultured with pericytes had markedly reduced expression of adhesion molecules (PECAM-1 and ICAM-1) and proinflammatory cytokines (CCL-2 and IL-6) in response to bacterial stimuli (Brucella ovis, Listeria monocytogenes, or Escherichia coli lipopolysaccharide). Pericyte-depleted mice intraperitoneally inoculated with either B. ovis, a stealthy pathogen that does not trigger detectable inflammation, or Listeria monocytogenes, developed peritonitis. Further, during Citrobacter rodentium infection, pericyte-depleted mice developed severe intestinal inflammation, which was not evident in control mice. The anti-inflammatory effect of pericytes required connexin 43, as either chemical inhibition or silencing of connexin 43 abrogated pericyte-mediated suppression of endothelial inflammatory responses. Our results define a mechanism by which pericytes modulate inflammation during infection, which shifts our understanding of pericyte biology: from a structural cell to a pro-active player in modulating inflammation. IMPORTANCE: A previously unknown mechanism by which pericytes modulate inflammation was discovered. The absence of pericytes or blocking interaction between pericytes and endothelium through connexin 43 results in stronger inflammation, which shifts our understanding of pericyte biology, from a structural cell to a player in controlling inflammation.

Impact of STING Inflammatory Signaling during Intracellular Bacterial Infections.

The early detection of bacterial pathogens through immune sensors is an essential step in innate immunity. STING (Stimulator of Interferon Genes) has emerged as a key mediator of inflammation in the setting of infection by connecting pathogen cytosolic recognition with immune responses. STING detects bacteria by directly recognizing cyclic dinucleotides or indirectly by bacterial genomic DNA sensing through the cyclic GMP-AMP synthase (cGAS). Upon activation, STING triggers a plethora of powerful signaling pathways, including the production of type I interferons and proinflammatory cytokines. STING activation has also been associated with the induction of endoplasmic reticulum (ER) stress and the associated inflammatory responses. Recent reports indicate that STING-dependent pathways participate in the metabolic reprogramming of macrophages and contribute to the establishment and maintenance of a robust inflammatory profile. The induction of this inflammatory state is typically antimicrobial and related to pathogen clearance. However, depending on the infection, STING-mediated immune responses can be detrimental to the host, facilitating bacterial survival, indicating an intricate balance between immune signaling and inflammation during bacterial infections. In this paper, we review recent insights regarding the role of STING in inducing an inflammatory profile upon intracellular bacterial entry in host cells and discuss the impact of STING signaling on the outcome of infection. Unraveling the STING-mediated inflammatory responses can enable a better understanding of the pathogenesis of certain bacterial diseases and reveal the potential of new antimicrobial therapy.

Comparison of Matrix-assisted Laser Desorption Ionization Time-of-flight Mass Spectrometry (MALDI-TOF MS) and the Vitek 2 System for Routine Identification of Clinically Relevant Bacteria and Yeast.

OBJECTIVE: In this study, we compared the observed agreement and correlation of the Vitek 2 system with the biomarker-based MALDI-TOF MS identification results of bacteria and yeast on a routine basis. METHODS: Clinical isolates collected from two years were included. Isolates were identified using the Vitek 2 system and MALDI-TOF MS. The percent of observed agreements and the kappa coefficient (κ) with its corresponding 95% interval confidence were calculated between both results. When species-level biotyper identifications matched a member of a group, complex, or one of the species of a slashing call, the identification was considered correct for agreement calculations. RESULTS: The 4,238 recruited isolates included 2,669 gram-negative bacteria, 1,479 gram-positive bacteria, and 90 yeast. Among gram-negative bacteria, the most frequent species identified were Escherichia coli (κ=0.983), Acinetobacter baumannii complex (κ=0.979), Klebsiella pneumoniae (κ=0.972), and Pseudomonas aeruginosa (κ=0.970). Among Staphylococcal species, Staphylococcus aureus was the most frequently species detected (κ=0.986), followed by S. epidermidis (κ=0.904). For enterococcal species, Enterococcus faecalis (κ=0.882) and Enterococcus faecium (κ=0.849) were the most frequently detected. For yeasts, the more common species were Candida albicans (κ=0.888), followed by Candida tropicalis (κ=0.946) and Candida glabrata (κ=1.000). CONCLUSIONS: According to our results, when antimicrobial susceptibility tests are performed using Vitek 2 cards, the most common pathogens are correctly identified for the most frequent clinical isolates.

Combination of herbal components (curcumin, carvacrol, thymol, cinnamaldehyde) in broiler chicken feed: Impacts on response parameters, performance, fatty acid profiles, meat quality and control of coccidia and bacteria.

The objective of this study was to determine whether curcumin and a commercial microencapsulated phytogenic supplement containing thymol, cinnamaldehyde and carvacrol in broiler chicken feed would improve health and meat quality (fatty acid profile), as well as to determine the coccidiostatic and bactericidal potential of the additives. The broiler chickens were divided into five groups: NC - negative control feed; PC - positive control; CU - with 50 mg/kg of curcumin, PHY - 100 mg/kg phytogenic; and PHY + CU, a combination of both additives at 50 mg/kg (curcumin) and 100 mg/kg (phytogenic). We observed significantly higher levels of total proteins associated with increased circulating globulins, as well as lower levels of uric acid, cholesterol and triglycerides in the PHY + CU group than in the NC. There were significantly fewer oocysts in birds supplemented with additives in the NC group on day 21; on day 35, the NC, PHY and PHY + CU groups had significantly lower counts than the PC and CU groups; however, at 44 days, the lowest counts were in PC group. The bacterial counts were significantly lower on day 21 in all groups that received additives than those of the control group; however, at 44 days, the bacterial and Escherichia coli counts in these groups were significantly higher than those of the control. Curcumin with or without phytogenic agent improved meat quality, with increased antioxidant levels and reduction of lipid peroxidation. There were significantly lower total saturated fatty acid levels and significantly greater monounsaturated/polyunsaturated fatty acid levels in broilers that consumed additives individually and in combination. The combination of additives significantly increased the crypt/villus ratio, a marker of improved intestinal health and performance. Additives potentiated their individual effects, suggesting they can replace conventional growth promoters without compromising health, intestinal mucosa or meat quality.

Quorum Sensing Interfering Strategies and Their Implications in the Management of Biofilm-Associated Bacterial Infections

Abstract The bacterial species employ various types of molecular communication systems recognized as quorum sensing for the synchronization of differential gene expression to regulate virulence traits and biofilm formation. A variety of quorum sensing inhibitors; molecules that interfere with quorum sensing among bacteria have been examined which can block the action of autoinducers. Moreover, the studies have scrutinized various enzymes for their quorum quenching activity resulting in the degradation of signaling molecules or blocking of gene expression. So far, the studies have found that these approaches are not only capable to reduce the pathogenicity and biofilm formation but also resulted in increased bacterial susceptibility to antibiotics and bacteriophages. The effectiveness of these strategies has been validated in different animal models and it seems that these practices will be transformed in near future to develop the medical devices including catheters, implants, and dressings for the prevention of bacterial infections. Although many of these approaches are still in the research stage, the increasing library of quorum quenching molecules and enzymes will open innovative perspectives for the development of antibacterial approaches which will extend the therapeutic arsenal against the pathogenic bacterial species.

Plasma and Renal Cortex Meropenem Concentrations in Patients Undergoing Percutaneous Renal Biopsy.

BACKGROUND: Urinary tract infection (UTI) is the most common bacterial infection in the world. Some cases can have serious complication as death by septic shock. With the increasing spread of multidrug-resistant bacteria, the therapeutic possibilities against the complicated UTI are exhausted, forcing the use of broad-spectrum antibiotics such as meropenem. OBJECTIVES: To evaluate the penetrating ability of meropenem to renal tissue using an enzymatic biosensor in samples of renal cortex and its correlation with plasma levels. METHOD: We conducted a descriptive study in humans with indication of kidney biopsy. Meropenem was administered 1 hour before performing the biopsy, and the concentrations of meropenem in a series of samples of plasma and renal biopsy were determined. RESULTS: Renal biopsy and plasma samples of 14 patients, 64% women with body mass index of 26.3 kg/m2 (SD ± 2.9) and estimated glomerular filtration rate of 57.5 mL/min/1.73 m2 (SD ± 44.1), were examined. Renal biopsy was done at 68.9 minutes (SD ± 20.3), and the second plasma sample was obtained at 82.1 minutes (SD ± 21.2) and the third at 149.6 minutes (SD ± 31.5). The mean kidney meropenem concentration was 3.1 µg/mL (SD ± 1.9). For each patient, a decay curve of plasma meropenem concentration was constructed. The proportion of meropenem concentrations in renal tissue and plasma at biopsy moment was 14% (SD ± 10) with an interquartile range of 5.5-20.3%. With normal renal function, meropenem can achieve a bactericidal effect towards bacteria with MIC-90 < 0.76 µg/mL in the renal parenchyma. CONCLUSIONS: Meropenem is effective to treat the most frequent uropathogens with the bactericidal effect. Nevertheless, for resistant bacteria, it is necessary to adjust the dose to achieve adequate parenchymal concentration.

Preferential usage of rifaximin for the treatment of hydrogen-positive smallintestinal bacterial overgrowth.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) is challenging to treat and diagnose and is associated with diagnosis of irritable bowel syndrome (IBS). Although no FDA-approved medications exist for treatment of SIBO, rifaximin has recently received approval to treat diarrhea-predominant IBS and patients with methane-positive SIBO breath tests. The aim of this study is to evaluate patient response to rifaximin for SIBO based on breath test results. MATERIALS AND METHODS: All patients underwent breath testing to evaluate for SIBO during a 42-month period. Patients were defined as having a positive glucose breath test for SIBO based on an increase of ≥ 20 ppm of hydrogen and/or ≥ 10 ppm of methane 90 minutes after ingesting glucose. Patient demographic and symptom data, antibiotic treatment regimens, symptomatic response to therapy, and repeat treatments were recorded. Institutional review board approval was obtained. RESULTS: A total of 53 of 443 patients had positive breath testing for SIBO. Response rates to rifaximin (550 mg three times daily for 14 days) were 47.4% for hydrogen positivity alone and 80% for both hydrogen and methane positivity. CONCLUSIONS: Rifaximin was the most commonly prescribed antibiotic regimen for SIBO therapy. Patients with hydrogen or hydrogen and methane positive breath tests responded well to rifaximin therapy. For patients with hydrogen-positive SIBO, rifaximin may prove a highly effective therapy in providing symptom relief from the effects of SIBO.

Preferential usage of rifaximin for the treatment of hydrogen-positive small intestinal bacterial overgrowth / Rifaximina como tratamiento de elección en pacientes con sobrecrecimiento bacteriano con prueba de hidrógeno positiva

Objectives: Small intestinal bacterial overgrowth (SIBO) is challenging to treat and diagnose and is associated with diagnosis of irritable bowel syndrome (IBS). Although no FDA-approved medications exist for treatment of SIBO, rifaximin has recently received approval to treat diarrhea-predominant IBS and patients with methane-positive SIBO breath tests. The aim of this study is to evaluate patient response to rifaximin for SIBO based on breath test results. Materials and methods: All patients underwent breath testing to evaluate for SIBO during a 42-month period. Patients were defined as having a positive glucose breath test for SIBO based on an increase of ≥ 20 ppm of hydrogen and/or ≥ 10 ppm of methane 90 minutes after ingesting glucose. Patient demographic and symptom data, antibiotic treatment regimens, symptomatic response to therapy, and repeat treatments were recorded. Institutional review board approval was obtained. Results: A total of 53 of 443 patients had positive breath testing for SIBO. Response rates to rifaximin (550 mg three times daily for 14 days) were 47.4% for hydrogen positivity alone and 80% for both hydrogen and methane positivity. Conclusions: Rifaximin was the most commonly prescribed antibiotic regimen for SIBO therapy. Patients with hydrogen or hydrogen and methane positive breath tests responded well to rifaximin therapy. For patients with hydrogen-positive SIBO, rifaximin may prove a highly effective therapy in providing symptom relief from the effects of SIBO.

Objetivos: El sobrecrecimiento bacteriano de intestino delgado es una entidad difícil de diagnosticar y tratar, frecuentemente asociada con el síndrome de intestino irritable. A pesar que la FDA no ha aprobado medicamentos para tratar el sobrecrecimiento bacteriano, la rifaximina ha sido recientemente aprobada para tratar el intestino irritable tipo diarrea y en pacientes con test de aliento metano positivo en sobrecrecimiento bacteriano. El objetivo del estudio fue evaluar la respuesta a rifaximina de los pacientes con sobrecremiento bacteriano con prueba de aliento positiva. Material y métodos: Todos los pacientes que se realizaron prueba de aliento por sobrecrecimiento bacteriano durante un periodo de 42 meses. Se definió un paciente con sobrecrecimiento bacteriano positivo si tenía un incremento mayor a 20 ppm de hidrógeno y/o 10 ppm de metano luego de 90 minutos de la ingesta de glucosa. Se registraron los datos demográficos, síntomas, tratamiento antibióticos recibidos, respuesta a la terapia, y repetición de tratamientos. Resultados: Un total de 53 de 443 pacientes tuvieron prueba de aliento positiva para sobrecrecimiento bacteriano. La tasa de respuesta a rifaximina (550 mg tres veces x día x 14 días) fue 47.4% para pacientes con sólo test de hidrógeno positivo, y 80% para pacientes con tanto test de hidrógeno como metano positivos. Conclusiones: La rifaximina es el régimen antibiótico más frecuentemente utilizado en sobrecrecimiento bacteriano. Los pacientes con prueba de aliento de hidrógeno o hidrógeno y metano positivos respondieron bien a la rifaximina. Para pacientes con sobrecrecimiento bacteriano prueba de hidrógeno positiva, la rifaximina puede ser una terapia efectiva en mejorar síntomas.

Guanylate-binding proteins at the crossroad of noncanonical inflammasome activation during bacterial infections.

The immune system is armed with a broad range of receptors to detect and initiate the elimination of bacterial pathogens. Inflammasomes are molecular platforms that sense a diverse range of microbial insults to develop appropriate host response. In that context, noncanonical inflammasome arose as a sensor for Gram-negative bacteria-derived LPS leading to the control of infections. This review describes the role of caspase-11/gasdermin-D-dependent immune response against Gram-negative bacteria and presents an overview of guanylate-binding proteins (GBPs) at the interface of noncanonical inflammasome activation. Indeed, caspase-11 acts as a receptor for LPS and this interaction elicits caspase-11 autoproteolysis that is required for its optimal catalytic activity. Gasdermin-D is cleaved by activated caspase-11 generating an N-terminal domain that is inserted into the plasmatic membrane to form pores that induce pyroptosis, a cell death program involved in intracellular bacteria elimination. This mechanism also promotes IL-1ß release and potassium efflux that connects caspase-11 to NLRP3 activation. Furthermore, GBPs display many features to allow LPS recognition by caspase-11, initiating the noncanonical inflammasome response prompting the immune system to control bacterial infections. In this review, we discuss the recent findings and nuances related to this mechanism and its biological functions.

Autophagy and Its Interaction With Intracellular Bacterial Pathogens.

Cellular responses to stress can be defined by the overwhelming number of changes that cells go through upon contact with and stressful conditions such as infection and modifications in nutritional status. One of the main cellular responses to stress is autophagy. Much progress has been made in the understanding of the mechanisms involved in the induction of autophagy during infection by intracellular bacteria. This review aims to discuss recent findings on the role of autophagy as a cellular response to intracellular bacterial pathogens such as, Streptococcus pyogenes, Mycobacterium tuberculosis, Shigella flexneri, Salmonella typhimurium, Listeria monocytogenes, and Legionella pneumophila, how the autophagic machinery senses these bacteria directly or indirectly (through the detection of bacteria-induced nutritional stress), and how some of these bacterial pathogens manage to escape from autophagy.

NOD2: Activation During Bacterial and Viral Infections, Polymorphisms and Potential as Therapeutic Target.

Nucleotide-binding domain (NBD) leucine-rich repeat (LRR)-containing receptors or NLRs are a family of receptors that detect both, molecules associated to pathogens and alarmins, and are located mainly in the cytoplasm. NOD2 belongs to the NLR family and is a dynamic receptor capable of interacting with multiple proteins and modulate immune responses in a stimuli-dependent manner. The experimental evidence shows that interaction between NOD2 structural domains and the effector proteins shape the overall response against bacterial or viral infections. Other reports have focused on the importance of NOD2 not only in infection but also in maintaining tissue homeostasis. However, not only protein interactions relate to function but also certain polymorphisms in the gene that encodes NOD2 have been associated with inflammatory diseases, such as Crohn's disease. Here, we review the importance and general characteristics of NOD2, discussing its participation in infections caused by bacteria and viruses as well as its interaction with other pathogen recognition receptors or effectors to induce antibacterial and antiviral responses. Finally, the role of NOD2 in chronic inflammatory conditions and its potential to be targeted therapeutically are examined.

Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors.

Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotic. Therefore, a deeper knowledge of the aminoglycoside-modifying enzymes and their interactions with the antibiotics and solvent is of paramount importance in order to facilitate the design of more effective and potent inhibitors and/or novel semisynthetic aminoglycosides that are not susceptible to modifying enzymes.

Prostaglandin E2 Mediates Cardiorespiratory Disturbances during Infection in Neonates.

OBJECTIVE: To determine whether infection, with associated eicosanoid release, is a main cause of respiratory disruption in neonates, by measuring levels of prostaglandin E2 (PGE2) and its metabolite (PGEM) in cerebrospinal fluid (CSF). STUDY DESIGN: Of 59 eligible infants, 25 preterm infants (mean gestational age, 28 ± 0.5 weeks) and 22 full-term infants (mean gestational age, 40 ± 0.5 weeks) from a level 3 neonatal intensive care unit and the general maternity neonatal ward were enrolled prospectively. Infants with a condition that can cause secondary apnea were excluded. Cardiorespiratory disturbances, such as apnea, bradycardia, and desaturation (ABD) events, were quantified. All infants were subjected to standard laboratory analysis of blood and CSF concentrations of biomarkers, including PGE2 and PGEM, within 24 hours of lumbar puncture, which were correlated with ABD events and culture-verified infections. RESULTS: PGEM levels were highest in infants with culture-verified sepsis and meningitis (P < .01). In infants without culture-verified bacterial infections, PGEM levels were higher in preterm infants compared with term infants (P < .05). The numbers of desaturation events and apnea events in neonates were positively associated with PGE2 levels in CSF (P < .05). CONCLUSION: PGE2 and PGEM are rapidly elevated in CSF during an infectious event and may explain cardiorespiratory disturbances, which are the major presenting symptoms of neonatal infections. PGE2 and PGEM are released during bacterial infections and could serve as biomarkers for sepsis and autonomic dysfunction in neonates.

Assessment of Apical Expression of Alpha-2 Integrin, Heat Shock Protein, and Proinflammatory and Immunoregulatory Cytokines in Response to Endodontic Infection.

INTRODUCTION: The purpose of this study was to examine alpha-2 integrin, molecular mediators, cytokines, and chemokines from cells in periapical interstitial fluid from root canal infections before and after the reduction of the bacterial load using a cleaning procedure. METHODS: Subjects included 20 patients referred to the School of Dentistry at the Universidade Federal de Minas Gerais (Belo Horizonte, Minas Gerais, Brazil). Clinical samples were taken from teeth with pulp necrosis, and no patients had acute periapical symptoms at the time of the appointments. After cleaning and drying, 3 paper points were introduced into the root canal, passing passively through the root apex (2 mm) into the periapical tissues for 1 minute. The samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize those gene expressions using real-time polymerase chain reaction. RESULTS: Significantly lower levels of tumor necrosis factor alpha, chemokine ligand 5 (CCL5), chemokine ligand 2/monocyte chemotactic protein 1 (CCL2/MCP-1), and interleukin (IL)-8 in teeth with restrained bacterial loads (second collection) compared with the first collection were observed (P < .05). Similarly, the messenger RNA expression of the integrins secreted phosphoprotein 1 (SSP1)/ostepontin and focal adhesion kinase (FAK) decreased in samples from the second collection (P < .05). The messenger RNA for the regulatory cytokine IL-10 was significant higher in samples from the second collection (day 7) compared with the first collection (day 0) (P < .05). Messenger RNA expression of IL-1ß, IL-17A, interferon gamma, alpha-2 integrin, and Hsp47/SERPINH1 were similar at both time points (P > .05). CONCLUSIONS: These findings suggest that after reducing the root canal bacterial load a decrease in the inflammatory response took place in the periapical lesions.

Elevated C-reactive protein and spontaneous bacterial peritonitis in children with chronic liver disease and ascites.

OBJECTIVES: The aims of this study were to compare laboratory indices of spontaneous bacterial peritonitis (SBP) and noninfected ascites in children with chronic liver disease and to determine the infectious agents involved in SBP. METHODS: The medical records of 90 children with chronic liver disease and ascites studied between January 2005 and August 2011 were reviewed for laboratory data of diagnostic significance in SBP. Standard laboratory tests included blood cell count, coagulation indices, liver and renal function tests, C-reactive protein (CRP), serum sodium concentration, serum albumin, and serum cultures. Ascitic fluid obtained from 152 paracentesis procedures was assayed for cytology, Gram stains, neutrophil counts, and bacteriological cultures. RESULTS: The SBP group manifested significantly lower albumin levels and elevated CRP levels, prothrombin times, international normalized ratios, and leukocyte number (P<0.05 in each case). CRP was shown to be an independent variable in the prediction of SBP. Values of serum creatinine, sodium concentration, urea, total bilirubin and differential leukocyte shift were comparable in SBP and noninfected ascites. Streptococcus pneumoniae was the most prevalent infectious agent in the ascitic fluid (44%). CONCLUSIONS: CRP may be useful in early detection and monitoring of SBP in children with liver disease.

Role of gap junctions and hemichannels in parasitic infections.

In vertebrates, connexins (Cxs) and pannexins (Panxs) are proteins that form gap junction channels and/or hemichannels located at cell-cell interfaces and cell surface, respectively. Similar channel types are formed by innexins in invertebrate cells. These channels serve as pathways for cellular communication that coordinate diverse physiologic processes. However, it is known that many acquired and inherited diseases deregulate Cx and/or Panx channels, condition that frequently worsens the pathological state of vertebrates. Recent evidences suggest that Cx and/or Panx hemichannels play a relevant role in bacterial and viral infections. Nonetheless, little is known about the role of Cx- and Panx-based channels in parasitic infections of vertebrates. In this review, available data on changes in Cx and gap junction channel changes induced by parasitic infections are summarized. Additionally, we describe recent findings that suggest possible roles of hemichannels in parasitic infections. Finally, the possibility of new therapeutic designs based on hemichannel blokers is presented.

Effectiveness of trimethoprim-sulfamethoxazole and metronidazole in the treatment of small intestinal bacterial overgrowth in children living in a slum.

Trimethoprim-sulfamethoxazole and metronidazole were used for 14 days to treat 20 children with small intestine bacterial overgrowth (SIBO). SIBO was diagnosed using the lactulose hydrogen breath test. The breath test was repeated 1 month after treatment, and 19 (95.0%) of 20 children showed no evidence of SIBO (P < 0.001). The area under the individual curves showed that children with SIBO exhibited greater hydrogen production before treatment in both the first hour and between 60 and 180 minutes after the breath test. The treatment did not decrease methane production. In conclusion, trimethoprim-sulfamethoxazole and metronidazole was effective in treating children with SIBO.