Background and Aims Crohn’s disease [CD] is associated with alterations in gut microbial composition and function. The present controlled-intervention study investigated the relationship between patterns of dietary intake and baseline gut microbiota in CD patients in remission and examined the effects of a dietary intervention in patients consuming a non-diversified diet [NDD]. Methods Forty outpatients with quiescent CD were recruited in Calgary, Alberta, Canada. Based on 3-day food records, patients consuming a lower plant-based and higher red and processed meat-based diet were assigned to the NDD group [n = 15] and received a 12-week structured dietary intervention; all other patients were assigned to the diversified diet [DD] control group [n = 25] and received conventional management. Faecal microbiota composition, short chain fatty acids [SCFAs] and calprotectin were measured. Results At baseline the NDD and DD groups had a different faecal microbial beta-diversity [p = 0.003, permutational multivariate analysis of variance]. The NDD group had lower Faecalibacterium and higher Escherichia/Shigella relative abundances compared to the DD group [3.3 ± 5.4% vs. 8.5 ± 10.6%; 6.9 ± 12.2% vs. 1.6 ± 4.4%; p ≤ 0.03, analysis of covariance]. These two genera showed a strong negative correlation [rs = −0.60, q = 0.0002]. Faecal butyrate showed a positive correlation with Faecalibacterium [rs = 0.52, q = 0.002], and an inhibitory relationship with Escherichia/Shigella abundance [four-parameter sigmoidal model, R = −0.83; rs = −0.44, q = 0.01], respectively. After the 12 weeks of dietary intervention, no difference in microbial beta-diversity between the two groups was observed [p = 0.43]. The NDD group demonstrated an increase in Faecalibacterium [p < 0.05, generalized estimated equation model], and resembled the DD group at the end of the intervention [p = 0.84, t-test with permutation]. We did not find an association of diet with faecal SCFAs or calprotectin. Conclusions Dietary patterns are associated with specific gut microbial compositions in CD patients in remission. A diet intervention in patients consuming a NDD modifies gut microbial composition to resemble that seen in patients consuming a DD. These results show that diet is important in shaping the microbial dysbiosis signature in CD towards a balanced community.
Multiplex electrochemical biosensors have been used for eliminating the matrix effect in complex bodily fluids or enabling the detection of two or more bioanalytes, overall resulting in more sensitive assays and accurate diagnostics. Many electrochemical biosensors lack reliable and low-cost multiplexing to meet the requirements of point-of-care detection due to either limited functional biosensors for multi-electrode detection or incompatible readout systems. We developed a new dual electrochemical biosensing unit accompanied by a customized potentiostat to address the unmet need for point-of-care multi-electrode electrochemical biosensing. The two-working electrode system was developed using screen-printing of a carboxyl-rich nanomaterial containing ink, with both working electrodes offering active sites for recognition of bioanalytes. The low-cost bi-potentiostat system (∼$80) was developed and customized specifically to the bi-electrode design and used for rapid, repeatable, and accurate measurement of electrochemical impedance spectroscopy signals from the dual biosensor. This binary electrochemical data acquisition (Bi-ECDAQ) system accurately and selectively detected SARS-CoV-2 Nucleocapsid protein (N-protein) in both spiked samples and clinical nasopharyngeal swab samples of COVID-19 patients within 30 min. The two working electrodes offered the limit of detection of 116 fg/mL and 150 fg/mL, respectively, with the dynamic detection range of 1–10,000 pg/mL and the sensitivity range of 2744–2936 Ω mL/pg.mm 2 for the detection of N-protein. The potentiostat performed comparable or better than commercial Autolab potentiostats while it is significantly lower cost. The open-source Bi-ECDAQ presents a customizable and flexible approach towards addressing the need for rapid and accurate point-of-care electrochemical biosensors for the rapid detection of various diseases.
Background: Fecal microbial transplantation (FMT) is used in the treatment of relapsing Clostridium difficile infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success. Results: Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of Klebsiella and Escherichia. A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage αdiversity and lower relative abundance compared to the donors of a failed initial FMT. Conclusions: In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.
There is growing interest in studying dietary fiber to stimulate microbiome changes that might prevent or alleviate inflammatory bowel disease (IBD). However, dietary fiber effects have shown varying degrees of efficacy, for reasons that are unclear. This study examined whether the effects of isomaltodextrin on gut microbiota and IBD were dependent on dose or host sex, using an Interleukin (IL)-10 deficient murine colitis model. After 12 weeks, colonic IL-12p70 was depressed in male mice receiving high-dose isomaltodextrin supplementation compared to the control group (p = 0.04). Male mice receiving high-dose isomaltodextrin exhibited changes in microbial alpha-diversity, including enhanced richness and evenness (p = 0.01) and limited reduction in the relative abundance of Coprococcus (q = 0.08), compared to the control group. These microbial compositional changes were negatively associated with IL-12p70 levels in the male group (rs ≤ −0.51, q ≤ 0.08). In contrast, female mice receiving isomaltodextrin displayed a reduction in alpha-diversity and Coprococcus abundance and a high level of IL-12p70, as did the control group. Together, these results indicate that isomaltodextrin altered the gut microbial composition linking specific immune-regulatory cytokine responses, while the interactions among fiber, microbiota and immune response were dose dependent and largely sex specific. The results further indicate that interactions between environmental and host factors can affect microbiome manipulation in the host.
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