Akkermansia muciniphila in the small intestine improves liver fibrosis in a murine liver cirrhosis model.

Recent evidence indicates that liver cirrhosis (LC) is a reversible condition, but there is no established intervention against liver fibrosis. Although the gut microbiota is considered involved in the pathogenesis of LC, the underlying mechanisms remain unclear. Although the antibiotic, rifaximin (RFX), is effective for hepatic encephalopathy (HE) with LC, the impact of RFX on intestinal bacteria is unknown. We investigated the bacterial compositions along the GI tract under RFX treatment using a murine LC model. RFX improved liver fibrosis and hyperammonemia and altered the bacterial composition in the small intestine. The efficacy of RFX was associated with increases in specific bacterial genera, including Akkermansia. Administration of a commensal strain of Akkermansia muciniphila improved liver fibrosis and hyperammonemia with changing bacterial composition in the small intestine. This study proposed a new concept "small intestine-liver axis" in the pathophysiology of LC and oral A. muciniphila administration is a promising microbial intervention.

Oxymatrine alleviates NSAID-associated small bowel mucosal injury by regulating MIP-1/CCR1 signalling and gut microbiota.

Oxymatrine (OMT) as a quinazine alkaloid extracted from matrine has been shown to exhibit anti-inflammatory and anti-tumour effects. However, the protective mechanism of OMT on NSAID-associated small bowel mucosal injury remains unreported. We found that OMT could improve the clinical symptoms and pathological inflammation scoring, reduce the secretion of proinflammatory cytokines IL-1ß, IL-6 and TNF-α and cell apoptosis, promote cell proliferation and protect intestinal mucosal barrier as compared with the Diclofenac Sodium (DS) group. Further RNA-seq and KEGG analysis uncovered that the differentially expressed genes between DS and control groups were mainly enriched in immune regulation, of which MIP-1γ and its receptor CCR1 expression were validated to be repressed by OMTH. MAPK/NF-κB as the MIP-1 upstream signalling was also inactivated by OMT treatment. In this study, OMT regulated gut microbiota. Venn diagrams visualized and identified 1163 shared OTUs between DS group and OMTH group. The results showed that the α diversity index in the DS group was lower than that in the OMTH group, indicating that the complexity of the flora was reduced in the intestinal inflammatory state. ß diversity mainly includes Principal Component Analysis (PCA) and Principal Co-ordinates Analysis (PCoA). The differences between groups can be observed through PCA. The more similar the composition of the flora, the closer the samples are. We found that the difference was smaller in the DS group than in the OMTH group. The results of PcoA showed that the sample similarity between OMTH groups was the highest. Moreover, gut microbiota analysis unveiled that the abundances of Ruminococcus 1, Oscillibacter and Prevotellaceae at the genus level as well as Lactobacillus SP-L-Yj at the species level were increased in OMTH group as compared with the DS group but the abundance of Allobaculum, Ruminococceos-UCG-005, Ruminococceos-NK4A214 and Clostridium associated with DS-induced small bowel mucosal injury could be decreased by OMTH. MIP-1α and CCR1 were upregulated in human small bowel injury samples as compared with the normal ileal mucosa tissues. In conclusion, our findings demonstrated that OMT could alleviate NSAID-associated small bowel mucosal injury by inhibiting MIP-1γ/CCR1 signalling and regulating gut microbiota.

Effects of 1-oleate-2-palmitate-3-linoleate glycerol supplementation on the small intestinal development and gut microbial composition of neonatal mice.

Recent studies have shown that 1-oleo-2-palmito-3-linoleyl glycerol (OPL) is the most abundant triacylglycerol in human breast milk in China. Epidemiologic studies have shown that sn-2 palmitate improves the absorption of fatty acids and calcium in infants. However, there have been few studies of the specific mechanism by which OPL affects intestinal function. In the present study, we have characterized the effects of various levels of OPL supplementation on the development of the intestinal epithelium and the intestinal microbiota of neonatal mice. OPL supplementation increased the body masses and intestinal lengths of weaned mice and promoted defecation. These positive effects were related to the effect of OPL to promote the development of intestinal villi and crypts. OPL increased the expression of the intestinal stem cell markers Olfm4 and Sox9 in the jejunum and ileum, which promoted their differentiation into goblet cells and Paneth cells. It also promoted the integrity of the epithelial barrier by increasing the secretion of mucin 2 and lysozyme 1 and the expression of the tight junction proteins occludin, ZO1, claudin 2, and claudin 3. More importantly, we found that low dose-OPL promotes the transformation of the intestinal microbiota of neonatal mice to the mature state in 3-month-old mice, increases the proportion of Firmicutes, and reduces the proportion of Bacteroidota. The proportions of anaerobic genera of bacteria, such as Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ligilactobacillus, and Bifidobacterium were higher, as were the key producers of short-chain fatty acids, such as Bacteroides and Blautia. OPL also increased the butyric acid content of the feces, which significantly correlated with the abundance of Lactobacillus. High-dose OPL tended to be more effective at promoting defecation and the development of the villi and crypts, but these effects did not significantly differ from those achieved using the lower dose. A low dose of OPL was more effective at increasing the butyric acid content and causing the maturation of microbes. In summary, the OPL supplementation of newborn mice promotes the establishment of the intestinal epithelial layer structure and barrier function, and also promotes the transformation of the intestinal microbiota to a mature state. This study lays a theoretical foundation for the inclusion of OPL in infant formula and provides a scientific basis for the development of intestinal health products.

Enteric pathogens relationship with small bowel histologic features of environmental enteric dysfunction in a multicountry cohort study.

BACKGROUND: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease. OBJECTIVES: The objective of this study was to determine if fecal enteropathogenic detection predicts subsequent EED histology. METHODS: Fecal samples were obtained from undernourished children aged <2 y without diarrhea enrolled in 3 cohort studies, who failed nutritional intervention and subsequently underwent endoscopy. Duodenal biopsies from 245 (Bangladesh n = 120, Pakistan n = 57, and Zambia n = 68) children were scored using a semiquantitative histologic grading protocol. Thirteen enteropathogens were sought in common across the 3 centers using TaqMan array cards (TAC) (Bangladesh and Pakistan) and the Luminex platform (Zambia). An additional 18 pathogens and 32 virulence loci were sought by TAC and included in sensitivity analyses restricted to TAC data. RESULTS: Multivariable linear regressions adjusting for study center, age at stool collection, and stool-to-biopsy interval demonstrated the following: 1) an association of norovirus and Shigella detection with subsequent enterocyte injury [ß 0.2 (95% CI: 0.1, 0.3); P = 0.002 and ß 0.2 (95% CI: 0.0, 0.3); P = 0.008, respectively], 2) association of Campylobacter with intraepithelial lymphocytes [ß 0.2 (95% CI: 0.0, 0.4); P = 0.046], and 3) association of Campylobacter and enterotoxigenic Escherichia coli with a summative EED histopathology index score [ß 4.2 (95% CI: 0.8, 7.7); P = 0.017 and ß 3.9 (95% CI: 0.5, 7.3); P = 0.027, respectively]. All but 2 of these associations (Shigella-enterocyte injury and Campylobacter-index score) were also demonstrated in TAC-only sensitivity analyses, which identified additional associations between other pathogens, pathogen burden, or virulence loci primarily with the same histologic parameters. CONCLUSIONS: The detection of some enteropathogens in asymptomatic infections is associated with subsequent EED histopathology. These novel findings offer a basis for future EED etiology and pathogenesis studies.

In vivo overexpression of the avian interleukin-17 in a necrotic enteritis disease model modulates the expression of antimicrobial peptides in the small intestine of broilers.

In humans and mice, the induction of interleukin (IL)-17 expression enhances epithelial barrier integrity through the secretion of antimicrobial peptides (AMP), thereby improving antibacterial defense. However, it is unclear whether IL-17 has similar antibacterial effects in chickens by modulating the expression of AMPs, such as avian beta-defensins (also known as gallinacins) and cathelicidins. This study evaluated the in vivo effects of inoculating 20-day-old broiler chickens with two doses of a plasmid encoding chicken IL-17 (pCDNA3.1/rchIL-17-V5-HIS TOPO plasmid [pCDNA3.1-IL-17]; 5 or 10 µg/bird). On day 23 of age, all broilers, except those in the negative control group, were orally challenged with a virulent Clostridium perfringens strain for three days. To investigate IL-17-mediated effects against C. perfringens infection, the expression of avian beta-defensin 1 (avBD1), avBD2, avBD4, avBD6, cathelicidins, and inducible nitric oxide synthase (iNOS) genes were quantified, and gross necrotic enteritis (NE) lesion scores were assessed in the small intestine. The results showed that broilers receiving the higher dose of pCDNA3.1-IL-17 (10 µg) had significantly lower NE lesion scores compared to those receiving the lower dose (5 µg), the vector control, and the positive control groups. Furthermore, the expression of all avian beta-defensins and cathelicidin genes was detectable across all groups, regardless of treatment and time points. IL-17 treatment led to significantly higher expression of avBD1, avBD2, avBD4, avBD6, cathelicidin, and iNOS in the duodenum, jejunum, and ileum compared to control chickens. In C. perfringens-infected chickens, the expression of avBD1, avBD2, avBD4, cathelicidin, and iNOS in the ileum was significantly higher than in control chickens. Pre-treatment with the higher dose of pCDNA3.1-IL-17 (10 µg) in infected chickens was associated with reduced NE lesion severity and increased expression of avBD1, avBD2, cathelicidin, and iNOS in the ileum, but not avBD4 and avBD6. These findings provide new insights into the potential effect of IL-17 and reduction in NE lesion severity by modulating AMP expression which may be involved in mediating protective immunity against intestinal infection with C. perfringens.

An Oral Botanical Supplement Improves Small Intestinal Bacterial Overgrowth (SIBO) and Facial Redness: Results of an Open-Label Clinical Study.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. OBJECTIVES: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. METHODS: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. RESULTS: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. CONCLUSIONS: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.

Concurrent Ascaris infection modulates host immunity resulting in impaired control of Salmonella infection in pigs.

Ascaris is one of the most widespread helminth infections, leading to chronic morbidity in humans and considerable economic losses in pig farming. In addition, pigs are an important reservoir for the zoonotic salmonellosis, where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoing Ascaris infection on the immune response to Salmonella in pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected with Salmonella alone. The impaired control of Salmonella in the coinfected pigs was associated with repressed interferon gamma responses in the small intestine and with the alternative activation of gut macrophages evident in elevated CD206 expression. Ascaris single and coinfection were associated with a rise of CD4-CD8α+FoxP3+ Treg in the lymph nodes draining the small intestine and liver. In addition, macrophages from coinfected pigs showed enhanced susceptibility to Salmonella infection in vitro and the Salmonella-induced monocytosis and tumor necrosis factor alpha production by myeloid cells was repressed in pigs coinfected with Ascaris. Hence, our data indicate that acute Ascaris infection modulates different immune effector functions with important consequences for the control of tissue-invasive coinfecting pathogens.IMPORTANCEIn experimentally infected pigs, we show that an ongoing infection with the parasitic worm Ascaris suum modulates host immunity, and coinfected pigs have higher Salmonella burdens compared to pigs infected with Salmonella alone. Both infections are widespread in pig production and the prevalence of Salmonella is high in endemic regions of human Ascariasis, indicating that this is a clinically meaningful coinfection. We observed the type 2/regulatory immune response to be induced during an Ascaris infection correlates with increased susceptibility of pigs to the concurrent bacterial infection.

The gastrointestinal microbiome, small bowel bacterial overgrowth, and microbiome modulators in cystic fibrosis.

People with cystic fibrosis (pwCF) have an altered gastrointestinal microbiome. These individuals also demonstrate propensity toward developing small intestinal bacterial overgrowth (SIBO). The dysbiosis present has intestinal and extraintestinal implications, including potential links with the higher rates of gastrointestinal malignancies described in CF. Given these implications, there is growing interest in therapeutic options for microbiome modulation. Alternative therapies, including probiotics and prebiotics, and current CF transmembrane conductance regulator gene modulators are promising interventions for ameliorating gut microbiome dysfunction in pwCF. This article will characterize and discuss the current state of knowledge and expert opinions on gut dysbiosis and SIBO in the context of CF, before reviewing the current evidence supporting gut microbial modulating therapies in CF.

Assessment of Biochemical, Inflammatory Biomarkers and Ultra-Processed Food Consumption in Children with Small Intestinal Bacterial Overgrowth: A Cross-Sectional Study.

OBJECTIVE: This study evaluated anthropometric, biochemical, and inflammatory biomarkers, as well as dietary intake in Brazilian children diagnosed with small intestinal bacterial overgrowth (SIBO) and compared them with their counterparts without SIBO. METHODS: This was a cross-sectional study with 106 children aged 7 to 10 years. A glucose-hydrogen breath test was performed to diagnose small intestinal bacterial overgrowth (SIBO). Anthropometric and dietary characteristics were assessed. Blood samples were collected and serum biochemical parameters and cytokines were measured. RESULTS: The occurrence of SIBO was 13.2%. Age, BMI, BMI/age WC, BFP, sex and biochemical markers were similar between SIBO-positive and SIBO-negative children (p > 0.05). High consumption of ultra-processed foods tended to be higher in SIBO-positive compared to SIBO-negative children (47.8 ± 8.2 vs. 42.6 ± 9.5, p = 0.06). Serum levels of IL-17 were higher in SIBO-positive than in SIBO-negative children [69.5 (5.4-125.7) vs. 53.4 (2.3-157.7), p = 0.03], while serum levels of IL-10 were lower in SIBO-positive than in SIBO-negative children [2.3 (0.6-7.2) vs. 5.7 (0.5-30.8), p = 0.04]. Finally, in a logistic regression adjusted for sex, BMI and age, consumption of ultra-processed foods (p = 0.03) and IL-6 levels (p = 0.003) were found to contribute to the occurrence of SIBO. CONCLUSION: this study identified for the first time an occurrence of 13% of SIBO in children living in the northeastern region of Brazil and showed that consumption of ultra-processed foods and serum levels of IL-6 may influence the occurrence of the SIBO in the pediatrics population.

Lining the small intestine with mycobacteriophages protects from Mycobacterium avium subsp. paratuberculosis and eliminates fecal shedding.

Johne's disease (JD), a chronic, infectious enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), affects wild and domestic ruminants. There is no cure or effective prevention, and current vaccines have substantial limitations, leaving this disease widespread in all substantial dairy industries causing economic, and animal welfare implications. Mycobacteriophages (MPs) have been gaining interest in recent years and are proposed as a promising solution to curtailing MAP infection. Using a well-validated infection model, we have demonstrated the preventative potential of MPs to protect dairy calves against MAP infection. Calves were supplemented daily with a phage cocktail from birth till weaning at 2 m of age and inoculated with MAP at 2 wk of age. Infection status was measured for 4.5 mo through blood, fecal, and postmortem tissue samples. Our findings highlight the remarkable efficacy of orally administered MPs. Notably, fecal shedding of MAP was entirely eliminated within 10 wk, in contrast to the infected control group where shedding continued for the entirety of the trial period. Postmortem tissue culture analysis further supported the effectiveness of MPs, with only 1 out of 6 animals in the phage-treated group testing positive for MAP colonized tissues compared to 6 out of 6 animals in the infected control group. Additionally, plaque assay results demonstrated the ability of phages to persist within the intestinal tract. Collectively, these results underscore the potential of orally administered MP cocktails as a highly effective intervention strategy to combat JD in dairy calves and by extension in the dairy industry.

[Small intestinal bacterial overgrowth (SIBO) - Therapy, nutrition, microbiome]. / Bakterielle Fehlbesiedlung des Dünndarms (SIBO) ­ Therapie, Ernährung, Mikrobiom.

SIBO (small intestinal bacterial overgrowth) is defined by bacterial overgrowth or colonization of the small intestine in combination with gastrointestinal symptoms such as bloating, nausea, pain, diarrhoea, malabsorption and food intolerance. SIBO can be caused by various mechanisms such as reduced intestinal motility, altered gastrointestinal anatomy, reduced gastric acid or pancreatic enzyme production, altered bile acid metabolism, or immune defects. Accordingly, SIBO often develops secondary to different underlying diseases.Diet has a fundamental influence on the composition of the intestinal microbiome and is therefore also a potential pathomechanism in SIBO. Furthermore, food intolerances are common in SIBO patients. However, both aspects have so far been insufficiently investigated. Nevertheless, elemental diets, carbohydrate-reduced diets, as well as pre- and probiotics are potential therapy options.This article provides a summary of current knowledge on the pathophysiology, diagnosis and treatment of SIBO, with particular emphasis on the role of nutrition and the microbiome.

Intestinal Methanogen Overgrowth (IMO) Is Associated with Delayed Small Bowel and Colonic Transit Time (TT) on the Wireless Motility Capsule (WMC).

BACKGROUND: Methanogens are associated with gut dysmotility in animal models but have not been robustly studied in humans. The WMC assesses regional transit time (TT) and pH in the GI tract. AIMS: To study the segmental TT and pH among patients with SIBO or IMO utilizing WMC. METHODS: We conducted a retrospective study of 207 patients who underwent a glucose or lactulose breath test (BT) and WMC from 2010 to 2022. Diagnosis of SIBO and IMO were based on the 2017 North American consensus criteria. TT and pH were extracted from WMC recordings. We tested for differences in means of continuous variables and frequencies of categorical variables using two-sample t tests, Wilcoxon Rank Sum test, Chi-square, and Fisher exact tests. We used R version 3.3.1 (2016-06-21) for all statistical analyses. RESULTS: A total of 196 patients met criteria, mean age 47.4 years and 155 (79.1%) females. Of the 86 (43.9%) patients with a positive BT, 42 (58.3%) had IMO only (meeting only CH4 criteria) and 30 (34.9%) met both H2 and CH4 criteria. Colonic TT was longer in patients with a positive BT compared to negative patients (40 h:29 min vs 28 h:51 min, p = 0.028). Small bowel TT and colonic TT were longer in patients with IMO compared to negative patients (SBTT: 5 h:15 min vs 4 h:32 min, p = 0.021; CTT: 44 h:23 min vs 28 h:51 min, p = 0.030). There were no significant differences in segmental pH compared to negative patients. CONCLUSION: To our knowledge, this is the largest study of patients who have undergone both BT and WMC. A positive BT was associated with delayed CTT, while having IMO only was associated with both delayed CTT and SBTT, but neither with pH. Future investigation is needed to elucidate whether changes in intestinal microbiota affect gut transit.

Intestinal microbial and metabolite profile in infants with small bowel stomas after bowel resection.

BACKGROUND: Infants with small bowel stomas (SBstoma) frequently struggle with absorption and rely on parenteral nutrition (PN). Intestinal absorption is difficult to predict based solely on intestinal anatomy. The purpose of this study was to characterize the microbiota and metabolic by-products within stoma effluent and correlate with clinical features and intestinal absorption. METHODS: Prospective cohort study collecting stoma samples from neonates with SBstoma (N = 23) or colostomy control (N = 6) at initial enteral feed (first sample) and before stoma closure (last sample). Gut bacteriome (16S ribosomal RNA [rRNA] sequencing), short-chain fatty acids (SCFAs) and bile acids (BAs) were characterized along with volume and energy content of a 48 h collection via bomb calorimetry (last sample). Hierarchical clustering and linear regression were used to compare the bacteriome and BAs/SCFAs, to bowel length, PN, and growth. RESULTS: Infants with ≤50% small bowel lost more fluid on average than those with >50% and controls (22, 18, 16 mL/kg/day, p = 0.013), but had similar energy losses (7, 10, 9 kcal/kg/day, p = 0.147). Infants growing poorly had enrichment of Proteobacteria compared to infants growing well (90% vs. 15%, p = 0.004). An increase in the ratio of secondary BAs within the small bowel over time, correlated with poor prognostic factors (≤50% small bowel, >50% of calories from PN, and poor growth). CONCLUSION: Infants with SBstoma and poor growth have a unique bacteriome community and those with poor enteral tolerance have metabolic differences compared to infants with improved absorption.

Mulberry polyphenols restored both small and large intestinal microflora in db/db mice, potentially alleviating type 2 diabetes.

Polyphenols in mulberry fruit have potential anti-diabetic effects by targeting the gut microbiota. This study investigated how mulberry polyphenols (MPs) influence the microbiota of the small and large intestines and their effects on type 2 diabetes symptoms. The results showed lower microbiota densities in the small intestine. MP treatments improved microbiota richness and diversity in both intestines, similar to metformin. In particular, at a 400 mg kg-1 dose, mulberry polyphenols decreased Firmicutes, Lactobacillus, and Bacilli, while increasing Bacteroidetes, leading to elevated propionate and butyrate levels. Less abundant small intestinal microbiota, like Enterobacterales, Mycoplasmatales, Enterobacteriaceae, and Ureaplasma, were involved in regulating blood glucose and insulin levels. Functional analysis suggested that mulberry polyphenols reshaped the small intestinal microbiota to influence blood glucose balance via unknown pathways, while in the large intestine, they primarily affected blood glucose through carbohydrate transport and metabolism. Based on their ability to regulate the composition of intestinal flora, MPs likely improved glucose homeostasis by enhancing glucose utilization, supporting pancreatic tissue health, and increasing serum antioxidant capacity. However, the specific mechanisms underlying this potential are yet to be fully explored. This study provides new insights into the influence of MPs on remodeling the microbiota residing in both the small and large intestines, which thereby may contribute to the improvement of the pathophysiology of type 2 diabetes.

A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery.

Bariatric surgical procedures such as sleeve gastrectomy (SG) provide effective type 2 diabetes (T2D) remission in human patients. Previous work demonstrated that gastrointestinal levels of the bacterial metabolite lithocholic acid (LCA) are decreased after SG in mice and humans. Here, we show that LCA worsens glucose tolerance and impairs whole-body metabolism. We also show that taurodeoxycholic acid (TDCA), which is the only bile acid whose concentration increases in the murine small intestine post-SG, suppresses the bacterial bile acid-inducible (bai) operon and production of LCA both in vitro and in vivo. Treatment of diet-induced obese mice with TDCA reduces LCA levels and leads to microbiome-dependent improvements in glucose handling. Moreover, TDCA abundance is decreased in small intestinal tissue from T2D patients. This work reveals that TDCA is an endogenous inhibitor of LCA production and suggests that TDCA may contribute to the glucoregulatory effects of bariatric surgery.

Aspergillus niger prolyl endopeptidase in celiac disease.

We comment here on the article by Stefanolo et al entitled "Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet", published in the World Journal of Gastroenterology. Celiac disease is a well-recognized systemic autoimmune disorder. In genetically susceptible people, the most evident damage is located in the small intestine, and is caused and worsened by the ingestion of gluten. For that reason, celiac patients adopt a gluten-free diet (GFD), but it has some limitations, and it does not prevent re-exposure to gluten. Research aims to develop adjuvant therapies, and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease (AN-PEP), which is able to degrade gluten in the stomach, reducing its concentration in the small intestine. The study found a high adherence to the GFD, but did not address AN-PEP as a gluten immunogenic peptide reducer, as it was only tested in patients following a GFD and not in gluten-exposing conditions. This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.

The relationship between small intestinal bacterial overgrowth and constipation in children - a comprehensive review.

Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations.

Monobutyrin Can Regulate the Gut Microbiota, Which Is Beneficial for the Development of Intestinal Barrier Function and Intestinal Health in Weaned Mice.

In this study, we investigated the effect of monobutyrin (MB) on the gut microbiota and intestinal health of weaned mice. MB was administered via gavage to 21-day-old weaned mice. Samples of small intestinal and ileal contents were collected on day 1, day 7, and day 21 post-administration. Seven days of MB administration enhanced the mucin layer and morphological structure of the intestine and the integrity of the intestinal brush border. Both MB and sodium butyrate (SB) accelerated tight junction development. Compared to SB, MB modulated intestinal T cells in a distinct manner. MB increased the ratio of Treg cells in the small intestine upon the cessation of weaning. After 21 days of MB administration, enhancement of the villus structure of the ileum was observed. MB increased the proportion of Th17 cells in the ileum. MB facilitated the transition of the small intestinal microbiota toward an adult microbial community structure and enhanced the complexity of the microbial community structure. An increase in Th17 cells enhanced intestinal barrier function. The regulatory effect of MB on Th17 cells may occur through the intestinal microbiota. Therefore, MB can potentially be used to promote intestinal barrier function, especially for weaning animals, with promising application prospects.

Effect of chronic stress on gel-forming mucins in the small intestine of BALB/c mice.

Intestinal homeostasis involves the collaboration of gut barrier components, such as goblet cells and IgA-microbiota complexes, that are under the control of stress that promotes inflammatory responses addressed primarily in the colon. The aim of this study was to evaluate the effect of stress on mucins, goblet cells, and proinflammatory parameters in the proximal and distal regions of the small intestine. A group (n = 6) of female 8-week-old BALB/c mice underwent board immobilization stress (2 h per day for 4 days) and were sacrificed with isoflurane. Samples from proximal and distal small segments were collected to analyze the following: 1) goblet cells stained with periodic acid-Schiff (PAS) and with alcian blue (AB) to visualize histologically neutral and acidic mucins, respectively; 2) IgA-microbiota complexes identified by flow cytometry in intestinal lavages; and 3) MUC2, MUC5AC, and IL-18 mRNA levels in whole mucosal scrapings by reverse transcription-qPCR. Regarding the unstressed group, in the proximal region of small intestine both PAS+ and AB+ goblet cells were unchanged; however, MUC5AC and IL-18 mRNA levels were increased, and the percentage of IgA-microbiota complexes was reduced. In the distal segment, the number of PAS+ goblet cells was increased, whereas the number of AB+ goblet cells was reduced and did not affect the remaining parameters. The data suggest that stress induces inflammation in the proximal small intestine; these findings may provide an experimental reference for human diseases that may affect the proximal small intestine, such as Crohn's disease, in which stress contributes to the progression of intestinal inflammation or relapse.