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.

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.

Identification of SIBO Subtypes along with Nutritional Status and Diet as Key Elements of SIBO Therapy.

Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane-dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy.

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.

Supplementation of a High-Fat Diet with Pentadecylresorcinol Increases the Representation of Akkermansia muciniphila in the Mouse Small and Large Intestines and May Protect against Complications Caused by Imbalanced Nutrition.

Imbalanced nutrition, such as a high-fat/high-carbohydrate diet, is associated with negative effects on human health. The composition and metabolic activity of the human gut microbiota are closely related to the type of diet and have been shown to change significantly in response to changes in food content and food supplement administration. Alkylresorcinols (ARs) are lipophilic molecules that have been found to improve lipid metabolism and glycemic control and decrease systemic inflammation. Furthermore, alkylresorcinol intake is associated with changes in intestinal microbiota metabolic activity. However, the exact mechanism through which alkylresorcinols modulate microbiota activity and host metabolism has not been determined. In this study, alterations in the small intestinal microbiota (SIM) and the large intestinal microbiota (LIM) were investigated in mice fed a high-fat diet with or without pentadecylresorcinol (C15) supplementation. High-throughput sequencing was applied for jejunal and colonic microbiota analysis. The results revealed that C15 supplementation in combination with a high-fat diet could decrease blood glucose levels. High-throughput sequencing analysis indicated that C15 intake significantly increased (p < 0.0001) the abundance of the probiotic bacteria Akkermansia muciniphila and Bifidobacterium pseudolongum in both the small and large intestines and increased the alpha diversity of LIM (p < 0.05), but not SIM. The preliminary results suggested that one of the mechanisms of the protective effects of alkylresorcinol on a high-fat diet is the modulation of the content of SIM and LIM and metabolic activity to increase the probiotic bacteria that alleviate unhealthy metabolic changes in the host.

Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury.

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

Antibiotics affect the pharmacokinetics of n-butylphthalide in vivo by altering the intestinal microbiota.

OBJECTIVE: N-butylphthalide (NBP) is a monomeric compound extracted from natural plant celery seeds, whether intestinal microbiota alteration can modify its pharmacokinetics is still unclear. The purpose of this study is to investigate the effect of intestinal microbiota alteration on the pharmacokinetics of NBP and its related mechanisms. METHODS: After treatment with antibiotics and probiotics, plasma NBP concentrations in SD rats were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The effect of intestinal microbiota changes on NBP pharmacokinetics was compared. Intestinal microbiota changes after NBP treatment were analyzed by 16S rRNA sequencing. Expressions of CYP3A1 mRNA and protein in the liver and small intestine tissues under different intestinal flora conditions were determined by qRT-PCR and Western Blot. KEGG analysis was used to analyze the effect of intestinal microbiota changes on metabolic pathways. RESULTS: Compared to the control group, the values of Cmax, AUC0-8, AUC0-∞, t1/2 in the antibiotic group increased by 56.1% (P<0.001), 56.4% (P<0.001), 53.2% (P<0.001), and 24.4% (P<0.05), respectively. In contrast, the CL and Tmax values decreased by 57.1% (P<0.001) and 28.6% (P<0.05), respectively. Treatment with antibiotics could reduce the richness and diversity of the intestinal microbiota. CYP3A1 mRNA and protein expressions in the small intestine of the antibiotic group were 61.2% and 66.1% of those of the control group, respectively. CYP3A1 mRNA and protein expressions in the liver were 44.6% and 63.9% of those in the control group, respectively. There was no significant change in the probiotic group. KEGG analysis showed that multiple metabolic pathways were significantly down-regulated in the antibiotic group. Among them, the pathways of drug metabolism, bile acid biosynthesis and decomposition, and fatty acid synthesis and decomposition were related to NBP biological metabolism. CONCLUSION: Antibiotic treatment could affect the intestinal microbiota, decrease CYP3A1 mRNA and protein expressions and increase NBP exposure in vivo by inhibiting pathways related to NBP metabolism.

A non-invasive tool to collect small intestine content in post weaning pigs: validation study.

The Capsule for Sampling (CapSa) is an ingestible capsule that collects small intestine content while transiting through the natural digestive pathway. In this study, 14 Swiss Large White pigs weighing less than 12 kg (Category < 12 kg) and 12 weighing between 12 and 20 kg (Category [12-20 kg]) were given two CapSas and monitored for three days. The animals were euthanized for post-mortem sampling, allowing us to directly obtain gut microbiota samples from the gastrointestinal tract. This post-mortem approach enabled a direct comparison between the microbial content from the gut and the samples collected via the CapSas, and it also facilitated precise identification of the CapSas' sampling sites within the gastrointestinal tract. For the category under 12 kg, only 2.3% of the administered CapSas were recovered from the feces. In contrast, in the 12-20 kg category, 62.5% of the CapSas were successfully retrieved from the feces within 48 h. Of these recovered CapSas, 73.3%-equating to 11 capsules from eight pigs-had a pH > 5.5 and were therefore selected for microbiome analysis. Bacterial composition of the CapSas was compared with that of the three segments of the small intestine, the large intestine and feces of the corresponding pig. The results were tested using a PERMANOVA model (Adonis) including sample type as a factor, and then pairwise comparisons were made. The bacterial composition found in the CapSas differed from that of the large intestine and feces (P < 0.01), while it did not differ from the first segment of the small intestine (P > 0.10). This study provides evidence that the CapSa effectively samples the intestinal microbiota from the upper section of the small intestine in post-weaning pigs. Furthermore, it was found that the collection of CapSas could only be successfully achieved in pigs classified within the heavier weight category.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Beneficial effect of heat-killed Lactiplantibacillus plantarum L-137 on intestinal barrier function of rat small intestinal epithelial cells.

Heat-killed Lactiplantibacillus plantarum L-137 (HK L-137) has been suggested to enhance the intestinal barrier in obese mice, leading to improvement of metabolic abnormalities and adipose tissue inflammation, and in healthy humans with overweight, leading to improvement of systemic inflammation. However, its detailed mechanism of action has not been clarified. Therefore, this study investigated the effects of HK L-137 on the permeability of rat small intestinal epithelial IEC-6 cells, tight junction-related gene and protein expression and localization, and intracellular signaling pathways involved in barrier function. Treatment of IEC-6 cells with HK L-137 for 26 h significantly reduced the permeability to fluorescein isothiocyanate-dextran (FD-4). HK L-137 also increased gene and protein expression of zonula occludens-1 (ZO-1), an important tight junction protein, without affecting the localization. Furthermore, inhibition of the extracellular signal-regulated kinase (ERK)1/2 pathway in IEC-6 cells canceled the HK L-137-related reduction in permeability to FD-4. Phosphorylation of ERK in IEC-6 cells was induced 15 min after the addition of HK L-137. These results suggest that HK L-137 reduces intestinal permeability partly through activating the ERK pathway and increasing expression of the ZO-1 gene and protein. Enhancement of intestinal barrier function with HK L-137 might be effective in preventing and treating leaky gut, for which no specific therapeutic tool has been established.

Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic.

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

Critical appraisal of the SIBO hypothesis and breath testing: A clinical practice update endorsed by the European society of neurogastroenterology and motility (ESNM) and the American neurogastroenterology and motility society (ANMS).

BACKGROUND: There is compelling evidence that microbe-host interactions in the intestinal tract underlie many human disorders, including disorders of gut-brain interactions (previously termed functional bowel disorders), such as irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) has been recognized for over a century in patients with predisposing conditions causing intestinal stasis, such as surgical alteration of the small bowel or chronic diseases, including scleroderma and is associated with diarrhea and signs of malabsorption. Over 20 years ago, it was hypothesized that increased numbers of small intestine bacteria might also account for symptoms in the absence of malabsorption in IBS and related disorders. This SIBO-IBS hypothesis stimulated significant research and helped focus the profession's attention on the importance of microbe-host interactions as a potential pathophysiological mechanism in IBS. PURPOSE: However, after two decades, this hypothesis remains unproven. Moreover, it has led to serious unintended consequences, namely the widespread use of unreliable and unvalidated breath tests as a diagnostic test for SIBO and a resultant injudicious use of antibiotics. In this review, we examine why the SIBO hypothesis remains unproven and, given the unintended consequences, discuss why it is time to reject this hypothesis and its reliance on breath testing. We also examine recent IBS studies of bacterial communities in the GI tract, their composition and functions, and their interactions with the host. While these studies provide important insights to guide future research, they highlight the need for further mechanistic studies of microbe-host interactions in IBS patients before we can understand their possible role in diagnosis and treatment of patient with IBS and related disorders.

Preservation of conjugated primary bile acids by oxygenation of the small intestinal microbiota in vitro.

Bile acids play a critical role in the emulsification of dietary lipids, a critical step in the primary function of the small intestine, which is the digestion and absorption of food. Primary bile acids delivered into the small intestine are conjugated to enhance functionality, in part, by increasing aqueous solubility and preventing passive diffusion of bile acids out of the gut lumen. Bile acid function can be disrupted by the gut microbiota via the deconjugation of primary bile acids by bile salt hydrolases (BSHs), leading to their conversion into secondary bile acids through the expression of bacterial bile acid-inducible genes, a process often observed in malabsorption due to small intestinal bacterial overgrowth. By modeling the small intestinal microbiota in vitro using human small intestinal ileostomy effluent as the inocula, we show here that the infusion of physiologically relevant levels of oxygen, normally found in the proximal small intestine, reduced deconjugation of primary bile acids, in part, through the expansion of bacterial taxa known to have a low abundance of BSHs. Further recapitulating the small intestinal bile acid composition of the small intestine, limited conversion of primary into secondary bile acids was observed. Remarkably, these effects were preserved among four separate communities, each inoculated with a different small intestinal microbiota, despite a high degree of taxonomic variability under both anoxic and aerobic conditions. In total, these results provide evidence for a previously unrecognized role that the oxygenated environment of the small intestine plays in the maintenance of normal digestive physiology. IMPORTANCE: Conjugated primary bile acids are produced by the liver and exist at high concentrations in the proximal small intestine, where they are critical for proper digestion. Deconjugation of these bile acids with subsequent transformation via dehydroxylation into secondary bile acids is regulated by the colonic gut microbiota and reduces their digestive function. Using an in vitro platform modeling the small intestinal microbiota, we analyzed the ability of this community to transform primary bile acids and studied the effect of physiological levels of oxygen normally found in the proximal small intestine (5%) on this metabolic process. We found that oxygenation of the small intestinal microbiota inhibited the deconjugation of primary bile acids in vitro. These findings suggest that luminal oxygen levels normally found in the small intestine may maintain the optimal role of bile acids in the digestive process by regulating bile acid conversion by the gut microbiota.

LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model.

Postnatal development of the gastrointestinal tract involves the establishment of the commensal microbiota, the acquisition of immune tolerance via a balanced immune cell composition, and maturation of the intestinal epithelium. While studies have uncovered an interplay between the first two, less is known about the role of the maturing epithelium. Here we show that intestinal-epithelial intrinsic expression of lysine-specific demethylase 1A (LSD1) is necessary for the postnatal maturation of intestinal epithelium and maintenance of this developed state during adulthood. Using microbiota-depleted mice, we find plasma cells, innate lymphoid cells (ILCs), and a specific myeloid population to depend on LSD1-controlled epithelial maturation. We propose that LSD1 controls the expression of epithelial-derived chemokines, such as Cxcl16, and that this is a mode of action for this epithelial-immune cell interplay in local ILC2s but not ILC3s. Together, our findings suggest that the maturing epithelium plays a dominant role in regulating the local immune cell composition, thereby contributing to gut homeostasis.

Glucose breath test for the detection of small intestine bacterial overgrowth: Impact of diet prior to the test.

BACKGROUND: Glucose breath test (GBT) is used for the diagnosis of small intestine bacterial overgrowth. A restrictive diet without fibers and/or fermentable food is recommended on the day before the test. The aim of our retrospective study was to evaluate the impact of two different restrictive diets on the results of GBT. METHODS: A change of the pretest restrictive diet was applied in our lab on September 1, 2020. The recommended diet was a fiber-free diet before this date, and a fiber-free diet plus restriction of all fermentable food afterward. We thus compared the results of GBT performed before (group A) and after (group B) this pretest diet modification. Demographics, reasons to perform GBT, digestive symptoms, and hydrogen and methane baseline values and variations after glucose ingestion were compared between the two groups. KEY RESULTS: 269 patients underwent GBT in group A, and 316 patients in group B. The two groups were comparable in terms of demographics. Methane and hydrogen baseline values were significantly higher in group A (respectively 14 [18] vs. 8 [14] ppm, p < 0.01 and 11 [14] vs. 6 [8] ppm, p < 0.01). The percentage of positive tests was higher in group A for methane (43% vs. 28%, p < 0.05), and for hydrogen (18% vs. 12%, p = 0.03). CONCLUSION & INFERENCES: This retrospective study suggests the importance of the restrictive diet prior to GBT. A strict limitation of fibers and fermentable food decreased hydrogen and methane baseline values, and the prevalence of positive GBT. Thus a strict restrictive diet should be recommended on the day before the test, in order to limit the impact of food on hydrogen and methane breath levels, and possibly improve the diagnosis quality of GBT.

The importance of food quality, gut motility, and microbiome in SIBO development and treatment.

The prevalence of small intestinal bacterial overgrowth (SIBO) is rising worldwide, particularly in nations with high rates of urbanization. Irritable bowel syndrome, inflammatory bowel illnesses, and nonspecific dysmotility are strongly linked to SIBO. Moreover, repeated antibiotic therapy promotes microorganisms' overgrowth through the development of antibiotic resistance. The primary cause of excessive fermentation in the small intestine is a malfunctioning gastrointestinal motor complex, which results in the gut's longer retention of food residues. There are anatomical and physiological factors affecting the functioning of the myoelectric motor complex. Except for them, diet conditions the activity of gastrointestinal transit. Indisputably, the Western type of nutrition is unfavorable. Some food components have greater importance in the functioning of the gastrointestinal motor complex than others. Tryptophan, an essential amino acid and precursor of the serotonin hormone, accelerates intestinal transit, and gastric emptying, similarly to fiber and polyphenols. Additionally, the effect of food on the microbiome is important, and diet should prevent bacterial overgrowth and exhibit antimicrobial effects against pathogens. Therefore, knowledge about proper nutrition is essential to prevent the development and recurrence of SIBO. Since the scientific world was unsure whether there was a long-term or potential solution for SIBO until quite recently, research on a number of the topics included in the article should be performed. The article aimed to summarize current knowledge about proper nutrition after SIBO eradication and the prevention of recurrent bacterial overgrowth. Moreover, a connection was found between diet, gut dysmotility, and SIBO.

Small intestinal bacterial overgrowth in diabetic gastroenteropathy.

BACKGROUND: Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. METHODS: In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. KEY RESULTS: Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006). CONCLUSIONS & INFERENCES: Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.

Microbiome changes under enteral deprivation are dynamic and dependent on intestinal location.

BACKGROUND: The microbiome has a pivotal role in intestinal health, and nutrition has a major role shaping its structure. Enteral deprivation, in which no oral/enteral nutrition is administered, is common in hospitalized/gastrointestinal patients. The dynamics that enteral deprivation exerts on the microbial community, specifically in the small intestine, are not well understood. METHODS: Enteral deprivation was modeled with exclusive parenteral nutrition (EPN) mice. Mice were allocated to receive either EPN or saline and chow (control) and euthanized after 0, 2, 4, or 6 days. DNA was extracted from jejunum, ileum, and colon content. 16S sequencing was used to compare changes in microbial communities between groups. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. RESULTS: EPN-treated mice showed community changes throughout the intestine. Beta diversity in colon showed clear separation between the groups (Bray-Curtis, P < 0.001). Time-dependent dynamics were seen in ileal but not jejunal samples. Alpha diversity was lower in the colon of EPN mice compared with control/baseline mice (Chao1, P < 0.01) but not in ileum/jejunum. Progressive loss of single-taxon domination was seen, most notably in the small intestine. This was accompanied by increases/decreases in specific taxa. A clear separation was seen in the functional capacity of the community between fed and enterally deprived mice at the ileum and colon, which was observed early on. CONCLUSIONS: Enteral deprivation disturbs the microbial community in a spatial and dynamic manner. There should be further focus on studying the effect of these changes on the host.

Small Intestine Bacterial Overgrowth is associated with increased Campylobacter and epithelial injury in duodenal biopsies of Bangladeshi children.

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter.