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Journal articleGroves HT, Higham SL, Moffatt MF, et al., 2020,
Respiratory viral infection alters the gut microbiota by inducing inappetence
, mBio, Vol: 11, ISSN: 2150-7511Respiratory viral infections are extremely common, but their impacts on the composition and function of the gut microbiota are poorly understood. We previously observed a significant change in the gut microbiota after viral lung infection. Here, we show that weight loss during respiratory syncytial virus (RSV) or influenza virus infection was due to decreased food consumption, and that the fasting of mice altered gut microbiota composition independently of infection. While the acute phase tumor necrosis factor alpha (TNF-α) response drove early weight loss and inappetence during RSV infection, this was not sufficient to induce changes in the gut microbiota. However, the depletion of CD8+ cells increased food intake and prevented weight loss, resulting in a reversal of the gut microbiota changes normally observed during RSV infection. Viral infection also led to changes in the fecal gut metabolome, with a significant shift in lipid metabolism. Sphingolipids, polyunsaturated fatty acids (PUFAs), and the short-chain fatty acid (SCFA) valerate were all increased in abundance in the fecal metabolome following RSV infection. Whether this and the impact of infection-induced anorexia on the gut microbiota are part of a protective anti-inflammatory response during respiratory viral infections remains to be determined.
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Journal articleGhani R, Mullish BH, Thursz M, et al., 2020,
Case-control study of recurrent Extended-Spectrum Beta Lactamase Enterobacteriaceae Urinary Tract Infections (ESBL UTIs): the management challenges
, Access Microbiology, Vol: 2 -
Journal articleGhani R, Mullish BH, Mcdonald J, et al., 2020,
Cohort study of Faecal Microbiota Transplantation for patient’s colonised with MDROs - successful prevention of invasive disease despite low decolonisation rates
, Access Microbiology, Vol: 2 -
Conference paperGhani R, Mullish BH, McDonald J, et al., 2020,
Disease prevention not decolonisation: a cohort study for faecal microbiota transplantation for patients colonised with multidrug-resistant organisms
, ECCMID 2020 -
Journal articleHarrison XA, Sewell T, Fisher M, et al., 2020,
Designing probiotic therapies with broad-spectrum activity against a wildlife pathogen
, Frontiers in Microbiology, Vol: 10, Pages: 1-11, ISSN: 1664-302XHost-associated microbes form an important component of immunity that protect against infection by pathogens. Treating wild individuals with these protective microbes, known as probiotics, can reduce rates of infection and disease in both wild and captive settings. However, the utility of probiotics for tackling wildlife disease requires that they offer consistent protection across the broad genomic variation of the pathogen that hosts can encounter in natural settings. Here we develop multi-isolate probiotic consortia with the aim of effecting broad-spectrum inhibition of growth of the lethal amphibian pathogen Batrachochytrium dendrobatidis (Bd) when tested against nine Bd isolates from two distinct lineages. Though we achieved strong growth inhibition between 70 and 100% for seven Bd isolates, two isolates appeared consistently resistant to inhibition, irrespective of probiotic strategy employed. We found no evidence that genomic relatedness of the chytrid predicted similarity of inhibition scores, nor that increasing the genetic diversity of the bacterial consortia could offer stronger inhibition of pathogen growth, even for the two resistant isolates. Our findings have important consequences for the application of probiotics to mitigate wildlife diseases in the face of extensive pathogen genomic variation.
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Journal articleSegal J, Mullish B, Clark S, et al., 2020,
P844 Higher proportions of genera and species in the Firmicutes phylum are associated with a healthy pouch compared with patients with chronic pouchitis
, Journal of Crohn's and Colitis, Vol: 14, Pages: S652-S652, ISSN: 1873-9946BackgroundStudies highlighting changes in bacterial composition in the ileoanal pouch are limited by heterogeneity in analysis techniques and sampling strategies Therefore, caution must be used when interpreting microbiota data. Similar to findings in IBD, a decrease in bacterial diversity and ‘dysbiosis’ are associated with acute and chronic inflammation in the pouch. Changes in Clostridium spp. and E. coli are associated with inflamed pouches and treatment response. This study aimed to compare the bacterial microbiota composition in patients with chronic pouchitis who responded to antibiotics vs. those who did not.MethodsPatients with confirmed chronic pouchitis defined by a pouch disease activity score ≥ 7 were treated with antibiotics. If patients were already on antibiotics, they were offered the opportunity to stop. Follow up was at 4 weeks to check clinical status. Patients who came off antibiotics who flared were given the opportunity to restart the antibiotics to prevent deterioration. Patients were analysed as either on antibiotics if they received antibiotics 2 weeks prior to the clinic or off antibiotics if they had stopped all antibiotics 2 weeks prior to follow-up. Stool was collected from patients on follow-up and DNA was extracted from this stool. Sequencing was performed on an Illumina platform. Statistical analysis was performed using STAMP 2.1.3 software with Welch’s two-sided t-test for comparing two groups with false discovery rate correction.ResultsThere were 28 patients in the cohort; 23 patients with chronic pouchitis and 5 healthy controls who had never had pouchitis. Ten patients were female. The median age of the cohort was 47 years (range 26–74 years). A total of 12 samples on antibiotics and 11 off antibiotics. There were 10 responders and 13 non-responders. There were no differences between responders and non-responders and no differences in those taking antibiotics vs. those not taking antibiotics with chroni
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Journal articleAllegretti JR, Mullish BH, 2020,
Faecal microbiota transplantations and urinary tract infections – Authors' reply
, The Lancet, Vol: 395, Pages: 271-271, ISSN: 0140-6736 -
Journal articleMcSweeney B, Allegretti JR, Fischer M, et al., 2020,
In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation.
, Gut Microbes, Vol: 11, Pages: 51-62Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.
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Journal articleCammarota G, Ianiro G, Kelly CR, et al., 2019,
International consensus conference on stool banking for faecal microbiota transplantation in clinical practice
, Gut, Vol: 68, Pages: 2111-2121, ISSN: 0017-5749<jats:p>Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent<jats:italic>Clostridioides difficile</jats:italic>infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.</jats:p><jats:p>Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,</jats:p><jats:p>Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.</jats:p>
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Journal articlePinato DJ, Gramenitskaya D, Altmann DM, et al., 2019,
Antibiotic therapy and outcome from immune-checkpoint inhibitors
, Journal for ImmunoTherapy of Cancer, Vol: 7
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