1.
Microbiome and Metabolome Profiles Associated With Different Types of Short Bowel Syndrome: Implications for Treatment.
Budinska, E, Gojda, J, Heczkova, M, Bratova, M, Dankova, H, Wohl, P, Bastova, H, Lanska, V, Kostovcik, M, Dastych, M, et al
JPEN. Journal of parenteral and enteral nutrition. 2020;(1):105-118
Abstract
BACKGROUND The gut microbiome and metabolome may significantly influence clinical outcomes in patients with short bowel syndrome (SBS). The study aimed to describe specific metagenomic/metabolomics profiles of different SBS types and to identify possible therapeutic targets. METHODS Fecal microbiome (FM), volatile organic compounds (VOCs), and bile acid (BA) spectrum were analyzed in parenteral nutrition (PN)-dependent SBS I, SBS II, and PN-independent (non-PN) SBS patients. RESULTS FM in SBS I, SBS II, and non-PN SBS shared characteristic features (depletion of beneficial anaerobes, high abundance of Lactobacilaceae and Enterobacteriaceae). SBS I patients were characterized by the abundance of oxygen-tolerant microrganisms and depletion of strict anaerobes. Non-PN SBS subjects showed markers of partial FM normalization. FM dysbiosis was translated into VOC and BA profiles characteristic for each SBS cohort. A typical signature of all SBS patients comprised high saturated aldehydes and medium-chain fatty acids and reduced short-chain fatty acid (SCFA) content. Particularly, SBS I and II exhibited low protein metabolism intermediate (indole, p-cresol) content despite the hypothetical presence of relevant metabolism pathways. Distinctive non-PN SBS marker was high phenol content. SBS patients' BA fecal spectrum was enriched by chenodeoxycholic and deoxycholic acids and depleted of lithocholic acid. CONCLUSIONS Environmental conditions in SBS gut significantly affect FM composition and metabolic activity. The common feature of diverse SBS subjects is the altered VOC/BA profile and the lack of important products of microbial metabolism. Strategies oriented on the microbiome/metabolome reconstitution and targeted delivery of key compounds may represent a promising therapeutic strategy in SBS patients.
2.
Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.
Smits, LP, Kootte, RS, Levin, E, Prodan, A, Fuentes, S, Zoetendal, EG, Wang, Z, Levison, BS, Cleophas, MCP, Kemper, EM, et al
Journal of the American Heart Association. 2018;(7)
Abstract
BACKGROUND Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. METHODS AND RESULTS We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. CONCLUSIONS Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR 4338.
3.
Bacteria, Bones, and Stones: Managing Complications of Short Bowel Syndrome.
Johnson, E, Vu, L, Matarese, LE
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2018;(4):454-466
Abstract
Short bowel syndrome (SBS) occurs in patients who have had extensive resection. The primary physiologic consequence is malabsorption, resulting in fluid and electrolyte abnormalities and malnutrition. Nutrient digestion, absorption, and assimilation may also be diminished by disturbances in the production of bile acids and digestive enzymes. Small bowel dilation, dysmotility, loss of ileocecal valve, and anatomical changes combined with acid suppression and antimotility drugs increase the risk of small intestinal bacterial overgrowth, further contributing to malabsorption. Metabolic changes that occur in SBS due to loss of colonic regulation of gastric and small bowel function can also lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and the eventual development of bone disease. Persistent inflammation, steroid use, parenteral nutrition, chronic metabolic acidosis, and renal insufficiency may exacerbate the problem and contribute to the development of osteoporosis. Multiple factors increase the risk of nephrolithiasis in SBS. In the setting of fat malabsorption, increased free fatty acids are available to bind to calcium, resulting in an increased concentration of unbound oxalate, which is readily absorbed across the colonic mucosa where it travels to the kidney. In addition, there is an increase in colonic permeability to oxalate stemming from the effects of unabsorbed bile salts. The risk of nephrolithiasis is compounded by volume depletion, metabolic acidosis, and hypomagnesemia, resulting in a decrease in renal perfusion, urine output, pH, and citrate excretion. This review examines the causes and treatments of small intestinal bacterial overgrowth, bone demineralization, and nephrolithiasis in SBS.