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1.
J Clin Invest ; 134(9)2024 Mar 21.
Article En | MEDLINE | ID: mdl-38512401

Bacterial translocation from the gut microbiota is a source of sepsis in susceptible patients. Previous work suggests that overgrowth of gut pathobionts, including Klebsiella pneumoniae, increases the risk of disseminated infection. Our data from a human dietary intervention study found that, in the absence of fiber, K. pneumoniae bloomed during microbiota recovery from antibiotic treatment. We thus hypothesized that dietary nutrients directly support or suppress colonization of this gut pathobiont in the microbiota. Consistent with our study in humans, complex carbohydrates in dietary fiber suppressed the colonization of K. pneumoniae and allowed for recovery of competing commensals in mouse models. In contrast, through ex vivo and in vivo modeling, we identified simple carbohydrates as a limiting resource for K. pneumoniae in the gut. As proof of principle, supplementation with lactulose, a nonabsorbed simple carbohydrate and an FDA-approved therapy, increased colonization of K. pneumoniae. Disruption of the intestinal epithelium led to dissemination of K. pneumoniae into the bloodstream and liver, which was prevented by dietary fiber. Our results show that dietary simple and complex carbohydrates were critical not only in the regulation of pathobiont colonization but also disseminated infection, suggesting that targeted dietary interventions may offer a preventative strategy in high-risk patients.


Dietary Carbohydrates , Gastrointestinal Microbiome , Klebsiella Infections , Klebsiella pneumoniae , Klebsiella pneumoniae/metabolism , Humans , Mice , Animals , Klebsiella Infections/microbiology , Klebsiella Infections/prevention & control , Dietary Carbohydrates/metabolism , Female , Male , Dietary Fiber/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/metabolism , Intestines/microbiology
2.
Cell Mol Gastroenterol Hepatol ; 17(1): 131-148, 2024.
Article En | MEDLINE | ID: mdl-37739064

BACKGROUND & AIMS: Altered plasma acylcarnitine levels are well-known biomarkers for a variety of mitochondrial fatty acid oxidation disorders and can be used as an alternative energy source for the intestinal epithelium when short-chain fatty acids are low. These membrane-permeable fatty acid intermediates are excreted into the gut lumen via bile and are increased in the feces of patients with inflammatory bowel disease (IBD). METHODS: Herein, based on studies in human subjects, animal models, and bacterial cultures, we show a strong positive correlation between fecal carnitine and acylcarnitines and the abundance of Enterobacteriaceae in IBD where they can be consumed by bacteria both in vitro and in vivo. RESULTS: Carnitine metabolism promotes the growth of Escherichia coli via anaerobic respiration dependent on the cai operon, and acetylcarnitine dietary supplementation increases fecal carnitine levels with enhanced intestinal colonization of the enteric pathogen Citrobacter rodentium. CONCLUSIONS: In total, these results indicate that the increased luminal concentrations of carnitine and acylcarnitines in patients with IBD may promote the expansion of pathobionts belonging to the Enterobacteriaceae family, thereby contributing to disease pathogenesis.


Enterobacteriaceae , Inflammatory Bowel Diseases , Animals , Humans , Enterobacteriaceae/metabolism , Dysbiosis , Inflammatory Bowel Diseases/microbiology , Carnitine/metabolism , Fatty Acids/metabolism , Escherichia coli , Biomarkers
3.
bioRxiv ; 2023 Jun 11.
Article En | MEDLINE | ID: mdl-37292978

Dysbiosis of the gut microbiota is increasingly appreciated as both a consequence and precipitant of human disease. The outgrowth of the bacterial family Enterobacteriaceae is a common feature of dysbiosis, including the human pathogen Klebsiella pneumoniae . Dietary interventions have proven efficacious in the resolution of dysbiosis, though the specific dietary components involved remain poorly defined. Based on a previous human diet study, we hypothesized that dietary nutrients serve as a key resource for the growth of bacteria found in dysbiosis. Through human sample testing, and ex-vivo , and in vivo modeling, we find that nitrogen is not a limiting resource for the growth of Enterobacteriaceae in the gut, contrary to previous studies. Instead, we identify dietary simple carbohydrates as critical in colonization of K. pneumoniae . We additionally find that dietary fiber is necessary for colonization resistance against K. pneumoniae , mediated by recovery of the commensal microbiota, and protecting the host against dissemination from the gut microbiota during colitis. Targeted dietary therapies based on these findings may offer a therapeutic strategy in susceptible patients with dysbiosis.

4.
Z Gastroenterol ; 61(2): 172-177, 2023 Feb.
Article En | MEDLINE | ID: mdl-36470286

BACKGROUND: Acute epiploic appendagitis is a rare differential diagnosis of unclear or acute abdomen. AIM: To describe - by means of a scientific case report - the extraordinary diagnosis of acute epiploic appendagitis along with contained diverticulitis and incarcerated herniation of the greater omentum into the hernial sac of a former trocar site (medical history, significant for laparoscopic ovarian cyst removal) in a 29-year-old female based on experiences obtained in the successful clinical case management, and on selective references from medical scientific literature. CASE SUMMARY: Medical history: A 29-year-old female was admitted with abdominal pain in the lower left quadrant. She reported a laparoscopic ovarian cyst removal 3 years prior. Physical examination of the abdomen revealed tenderness in the lower left quadrant without a palpable mass.Leading diagnoses were found using transabdominal ultrasound and confirmed by an abdominal CT scan; namely, incarcerated trocar hernia, diverticulitis of sigmoid colon, and acute epiploic appendagitis. Therapeutic approach was comprised of an explorative laparoscopy (because of the incarcerated hernia), adhesiolysis, removal of a tip of the greater omentum out of the hernial sac, closure of the hernial orifice, and removal of an unclear, inflamed, and bloody fatty tissue from the wall of the descending colon (histopathological investigation confirmed acute epiploic appendagitis). This was flanked by conservative treatment of diverticulitis of the sigmoid colon.Further clinical course was uneventful, with discharge on the 3rd postoperative day with favorable long-term outcome, characterized by no further complaints for 15 months. DISCUSSION: Acute epiploic appendagitis is an inflammatory, usually self-limiting condition of the epiploic appendages of the colon. It typically manifests with abdominal pain in the lower left quadrant. Imaging is an important diagnostic tool to determine whether the patient has, in fact, acute epiploic appendagitis, so recognizing the characteristic oval lesions with the surrounding inflammation and central fat attenuation on CT, as well as the hyperechoic oval lesions with a hypoechoic peripheral band on ultrasound images is crucial. Nevertheless, it is often overlooked in patients and confused with other differential diagnoses, such as appendicitis or diverticulitis. Although the condition appears infrequently, it is essential to be proficient in the diagnostic evaluation, as a misdiagnosis may lead to unnecessary treatment and even surgical intervention. IN CONCLUSION: , the patient was initially diagnosed with an incarcerated abdominal hernia, and therefore subsequently underwent surgery. The inflamed epiploic appendage was discovered in laparoscopic exploration, removed, and confirmed through the histopathology report. This is an approach to be performed with great caution so as not to 1. : misinterpret an inflamed diverticula or covered perforation of it as well as not 2. : overlooking a peritoneal tumor lesion.


Abdomen, Acute , Diverticulitis , Ovarian Cysts , Female , Humans , Adult , Abdomen, Acute/diagnosis , Abdomen, Acute/etiology , Abdomen, Acute/surgery , Diagnosis, Differential , Abdominal Pain/etiology , Diverticulitis/diagnosis , Hernia/complications , Hernia/diagnosis , Ovarian Cysts/complications , Ovarian Cysts/diagnosis
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