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Investigating the gut microbiome and metabolome frequently requires faecal samples, which can be difficult to obtain. Previous studies have shown that rectal swabs are comparable to faecal samples for analysing gut microbiota composition and key metabolites. In this study, 3D printed rectal swabs were compared with conventional flocked swabs and faecal samples, due to the potential advantages 3D printing as a technique offers for swab production and development. 16S rRNA gene sequencing, qPCR and metabolite profiling (using 1 H-NMR spectroscopy) were performed on swab and faecal samples from healthy participants. Faecal calprotectin and total protein analysis were performed on samples from inflammatory bowel disease (IBD) patients. There were no significant differences between both swab types and faecal samples when assessing key measures of alpha and beta diversity, and differences in the abundance of major phyla. There was a strong correlation between both swab types and faecal samples for all combined metabolites detected by NMR. In IBD patients, there was no significant difference in faecal calprotectin and total protein levels between both swab types and faecal samples. These data lead us to conclude that 3D printed swabs are equivalent to flocked swabs for the analysis of the gut microbiome, metabolome and inflammation., (© 2024. The Author(s).)

Background and Aims: We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with inflammatory bowel disease [IBD]., Methods: We conducted a prospective study including 213 IBD patients and 53 healthy controls: 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab, or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination, and interval between vaccination and sampling., Results: Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (geometric mean ratio 0.35 [95% confidence interval 0.20-0.60], p = 0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p = 0.0050), and tofacitinib (0.28 [0.14-0.57], p = 0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p = 0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p = 0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p = 0.017), and tofacitinib (0.23 [0.10-0.56], p = 0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 [r = 0.27; p = 0.0004] and H1N1 [r = 0.33; p < 0.0001]., Conclusions: Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to influenza/A, similar to COVID-19 vaccine-induced antibody responses., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Climate change is predicted to cause milder winters and thus exacerbate soil freeze-thaw perturbations in the subarctic, recasting the environmental challenges that soil microorganisms need to endure. Historical exposure to environmental stressors can facilitate the microbial resilience to new cycles of that same stress. However, whether and how such microbial memory or stress legacy can modulate microbial responses to cycles of frost remains untested. Here, we conducted an in situ field experiment in a subarctic birch forest, where winter warming resulted in a substantial increase in the number and intensity of freeze-thaw events. After one season of winter warming, which raised mean surface and soil (-8 cm) temperatures by 2.9 and 1.4°C, respectively, we investigated whether the in situ warming-induced increase in frost cycles improved soil microbial resilience to an experimental freeze-thaw perturbation. We found that the resilience of microbial growth was enhanced in the winter warmed soil, which was associated with community differences across treatments. We also found that winter warming enhanced the resilience of bacteria more than fungi. In contrast, the respiration response to freeze-thaw was not affected by a legacy of winter warming. This translated into an enhanced microbial carbon-use efficiency in the winter warming treatments, which could promote the stabilization of soil carbon during such perturbations. Together, these findings highlight the importance of climate history in shaping current and future dynamics of soil microbial functioning to perturbations associated with climate change, with important implications for understanding the potential consequences on microbial-mediated biogeochemical cycles., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

The microbial use of resources to sustain life and reproduce influences for example, decomposition and plant nutrient provisioning. The study of "limiting factors" has shed light on the interaction between plants and their environment. Here, we investigated whether carbon (C), nitrogen (N), or phosphorus (P) was limiting for soil microorganisms in a subarctic tundra heath, and how changes in resource availability associated with climate change affected this. We studied samples in which changes in resource availability due to climate warming were simulated by the addition of birch litter and/or inorganic N. To these soils, we supplied factorial C (as glucose), N (as NH 4 NO 3 ), and P (as KH 2 PO 4 /K 2 HPO 4 ) additions ("limiting factor assays," LFA), to determine the limiting factors. The combination of C and P induced large growth responses in all soils and, combined with a systematic tendency for growth increases by C, this suggested that total microbial growth was primarily limited by C and secondarily by P. The C limitation was alleviated by the field litter treatment and strengthened by N fertilization. The microbial growth response to the LFA-C and LFA-P addition was strongest in the field-treatment that combined litter and N addition. We also found that bacteria were closer to P limitation than fungi. Our results suggest that, under a climate change scenario, increased C availability resulting from Arctic greening, treeline advance, and shrubification will reduce the microbial C limitation, while increased N availability resulting from warming will intensify the microbial C limitation. Our results also suggest that the synchronous increase of both C and N availability might lead to a progressive P limitation of microbial growth, primarily driven by bacteria being closer to P limitation. These shifts in microbial resource limitation might lead to a microbial targeting of the limiting element from organic matter, and also trigger competition for nutrients between plants and microorganisms, thus modulating the productivity of the ecosystem., (© 2023 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Soil microbial communities play a pivotal role in regulating ecosystem functioning. But they are increasingly being shaped by human-induced environmental change, including intense "pulse" perturbations, such as droughts, which are predicted to increase in frequency and intensity with climate change. While it is known that soil microbial communities are sensitive to such perturbations and that effects can be long-lasting, it remains untested whether there is a threshold in the intensity and frequency of perturbations that can trigger abrupt and persistent transitions in the taxonomic and functional characteristics of soil microbial communities. Here we demonstrate experimentally that intense pulses of drought equivalent to a 30-year drought event (<15% WHC) induce a major shift in the soil microbial community characterised by significantly altered bacterial and fungal community structures of reduced complexity and functionality. Moreover, the characteristics of this transformed microbial community persisted after returning soil to its previous moisture status. As a result, we found that drought had a strong legacy effect on bacterial community function, inducing an enhanced growth rate following subsequent drought. Abrupt transitions are widely documented in aquatic and terrestrial plant communities in response to human-induced perturbations. Our findings demonstrate that such transitions also occur in soil microbial communities in response to high intensity pulse perturbations, with potentially deleterious consequences for soil health., (© 2023. The Author(s).)

Background: Patients with inflammatory bowel disease (IBD) receiving anti-TNF and JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the Omicron BA.4/5 variant., Methods: In this multicentre cohort study, we prospectively recruited 340 adults (69 healthy controls and 271 IBD) at nine UK hospitals between May 28, 2021 and March 29, 2022. The IBD study population was established (>12 weeks therapy) on either thiopurine (n = 63), infliximab (n = 45), thiopurine and infliximab combination therapy (n = 48), ustekinumab (n = 45), vedolizumab (n = 46) or tofacitinib (n = 24). Patients were excluded if they were being treated with any other immunosuppressive therapies. Participants had two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccines, followed by a third dose of either BNT162b2 or mRNA1273. Pseudo-neutralisation assays against SARS-CoV-2 wild-type and BA.4/5 were performed. The half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARS-CoV-2 neutralising response against wild-type virus and Omicron BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, vaccine type, age, and interval between vaccination and blood collection. This study is registered with ISRCTN (No. 13495664)., Findings: Both heterologous (first two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both wild-type SARS-CoV-2 virus and the Omicron BA.4/5 variant in healthy participants and patients with IBD. Antibody titres against BA.4/5 were significantly lower than antibodies against wild-type virus in both healthy participants and patients with IBD (p < 0.0001). Multivariable models demonstrated that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in patients with IBD on infliximab (Geometric Mean Ratio (GMR) 0.19 [0.10, 0.36], p < 0.0001), infliximab and thiopurine combination (GMR 0.25 [0.13, 0.49], p < 0.0001) or tofacitinib (GMR 0.43 [0.20, 0.91], p = 0.028), but not in patients on thiopurine monotherapy, ustekinumab, or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against wild-type (p = 0.037) and BA.4/5 (p = 0.045)., Interpretation: A third dose of a COVID-19 mRNA vaccine based on the wild-type spike glycoprotein significantly boosts neutralising antibody titres in patients with IBD. However, responses are lower against the Omicron variant BA.4/5, particularly in patients taking anti-TNF and JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed patients with IBD may receive additional benefit from bivalent vaccine boosters which target Omicron variants., Funding: Pfizer., Competing Interests: ALH reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Arena, Atlantic, Bristol Myers Squibb, Celltrion, Ferring, Dr Falk, Galapagos, Janssen, MSD, Napp, Pfizer, Pharmacosmos, Shire, and Takeda; participation on the Global Steering Committee for Genentech. AJK reports consulting fees from Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer and Takeda; support for attending meetings or travel from Janssen, Tillotts, and Norgine; and participation in a data safety monitoring board or advisory board for AbbVie. CWL received personal consulting fees from Galapagos, AbbVie, Takeda, Pfizer, Janssen and Iterative Scopes; institutional consulting fees from Trellus Health; and support for attending meetings from Galapagos, AbbVie, Takeda, Pfizer, Janssen, GSK, Gilead, Fresenius Kabi, Ferring, and Dr Falk. GRJ received speaker fees from Takeda, Ferring, Janssen, AbbVie and Fresenius Kabi. JLA received support for attending meetings from Takeda. JRG reports grants from Roche, Biogen, Celltrion Healthcare, Takeda and Galapagos. KVP received consulting fees from AbbVie, Janssen, Galapagos and Pfizer; reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Dr Falk, Janssen, Galapagos, Pfizer, Takeda, Tillotts and Ferring; support for attending meetings or travel from AbbVie, Dr Falk, Janssen, Galapagos, Pfizer, Takeda, Tillotts and Ferring; and participation on a data safety monitoring board or advisory board for AbbVie, Galapagos, Pfizer and Janssen. SB received research grant from Bowel Research UK and support for attending conferences from Ferring and Dr Falk, outside the submitted work. KMP is a member of the data safety monitoring board for NCT05249829 and NCT05575492; has received a fee for speaking from Seqirus and Sanofi Pasteur, and has research funding from the Chan Zuckerberg Initiative, the MRC/UKRI, the Vaccine Task Force, and NIHR Imperial BRC outside the submitted work. KK reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen and Ferring; support for attending meetings or travel from Janssen and Takeda; and participation on a data safety monitoring board or advisory board for Janssen and PredictImmune. MP received research grant from Pfizer and speaker fees from Janssen. NAK reports grants from AbbVie, Biogen, Celgene, Celltrion, Galapagos, MSD, Napp, Pfizer, Pharmacosmos, Roche, and Takeda; consulting fees from Amgen, Bristol Myers Squibb, Dr Falk, Janssen, Mylan, Pharmacosmos, Galapagos, Takeda, and Tillotts; personal fees from Allergan, Celltrion, Dr Falk, Ferring, Janssen, Pharmacosmos, Takeda, Tillotts, and Galapagos; and support for attending meetings from AbbVie, Dr Falk, Tillotts and Janssen, outside the submitted work. PMI reports grants from Celltrion, Takeda, MSD, Pfizer, and Galapagos; personal fees from Gilead, Pfizer, Galapagos, Takeda, AbbVie, Celltrion, Janssen, Bristol Myers Squibb, Lilly, and Arena; speaker fees from Pfizer, Galapagos, Takeda, AbbVie, Celltrion, Janssen, Bristol Myers Squibb, Lilly, and Arena, outside the submitted work. SS reports grants from Tillotts, Takeda, Janssen, Pfizer and AbbVie; received personal fees from AbbVie, Tillotts, Janssen, Takeda, Dr Falk, Lilly and Bristol Myers Squibb; received support for attending meetings from Janssen, AbbVie and Celltrion; and serves as a member of the data safety monitoring board for AbbVie, Janssen, Takeda, Celltrion, Lilly and Bristol Myers Squibb. TA reports grant funding from Pfizer to deliver this study; grants from Celltrion, Roche, Takeda, Biogen, and Galapagos; and honoraria for lectures from Takeda and Roche, outside the submitted work. NP is the principal investigator on the research grant from Pfizer that funded the VIP study; has received research grants from Bristol Myers Squibb, Roche, Biogen, Celltrion Healthcare, Takeda, Galapagos, CCUK, AstraZeneca, Helmsley Charitable Trust, outside the submitted work; reports personal fees from Takeda, Janssen, Pfizer, Galapagos, Bristol Myers Squibb, AbbVie, Roche, Lilly, Allergan, Celgene and AstraZeneca outside the submitted work; and has served as a speaker or advisory board member for AbbVie, Allergan, Bristol Myers Squibb, Celgene, Dr Falk, AstraZeneca, Galapagos and Vifor; and serves as a member of the data safety monitoring board for Bristol Myers Squibb and AstraZeneca. All other authors declare no competing interests., (© 2023 The Author(s).)

Remediation of soil contaminated with cadmium (Cd) and lead (Pb) is critical for tobacco production. Silicon (Si) fertilizer can relieve heavy metal stress and promote plant growth, however, it remains unknown whether fertilization with Si can mitigate the effects of Cd and Pb on tobacco growth and alter microbial community composition in polluted soils. Here we assessed the effect of two organic (OSiFA, OSiFB) and one mineral Si fertilizer (MSiF) on Cd and Pb accumulation in tobacco plants, together with responses in plant biomass, physiological parameters and soil bacterial communities in pot experiments. Results showed that Si fertilizer relieved Cd and Pb stress on tobacco, thereby promoting plant growth: Si fertilizer reduced available Cd and Pb in the soil by 37.3 % and 28.6 %, respectively, and decreased Cd and Pb contents in the plant tissue by 42.0-55.5 % and 17.2-25.6 %, resulting in increased plant biomass by 13.0-30.5 %. Fertilization with Si alleviated oxidative damage by decreasing malondialdehyde content and increasing peroxidase and ascorbate peroxidase content. In addition, Si fertilization increased photosynthesis, chlorophyll and carotenoid content. Microbial community structure was also affected by Si fertilization. Proteobacteria and Actinobacteria were the dominant phylum in the Cd and Pb contaminated soils, but Si fertilization reduced the abundance of Actinobacteria. Si fertilization also altered microbial metabolic pathways associated with heavy metal resistance. Together, our results suggest that both organic and mineral Si fertilizers can promote tobacco growth by relieving plant physiological stress and favoring a heavy metal tolerant soil microbial community., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic offered a unique opportunity to understand inflammatory bowel disease (IBD) management during unexpected disruption. This could help to guide practice overall., Aims: To compare prescribing behaviour for IBD flares and outcomes during the early pandemic with pre-pandemic findings METHODS: We performed an observational cohort study comprising patients who contacted IBD teams for symptomatic flares between March and June 2020 in 60 National Health Service trusts in the United Kingdom. Data were compared with a pre-pandemic cohort after propensity-matching for age and physician global assessment of disease activity., Results: We included 1864 patients in each of the pandemic and pre-pandemic cohorts. The principal findings were reduced systemic corticosteroid prescription during the pandemic in Crohn's disease (prednisolone: pandemic 26.5% vs. 37.1%; p < 0.001) and ulcerative colitis (UC) (prednisolone: pandemic 33.5% vs. 40.7%, p < 0.001), with increases in poorly bioavailable oral corticosteroids in Crohn's (pandemic 15.6% vs. 6.8%; p < 0.001) and UC (pandemic 11.8% vs. 5.2%; p < 0.001). Ustekinumab (Crohn's and UC) and vedolizumab (UC) treatment also significantly increased. Three-month steroid-free remission in each period was similar in Crohn's (pandemic 28.4% vs. 32.1%; p = 0.17) and UC (pandemic 36.4% vs. 40.2%; p = 0.095). Patients experiencing a flare and suspected COVID-19 were more likely to have moderately-to-severely active disease at 3 months than those with a flare alone., Conclusions: Despite treatment adaptations during the pandemic, steroid-free outcomes were comparable with pre-pandemic levels, although concurrent flare and suspected COVID-19 caused worse outcomes. These findings have implications for IBD management during future pandemics and for standard practice., (© 2022 John Wiley & Sons Ltd.)

Background: COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose., Methods: VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28-49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data., Findings: Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p<0·0001), infliximab plus thiopurine (1818·3 U/mL [6·7]; p<0·0001), and tofacitinib (8071·5 U/mL [3·1]; p=0·0018) compared with the healthy control group (16 774·2 U/mL [2·6]). There were no significant differences in anti-SARS-CoV-2 S1 RBD antibody concentrations between the healthy control group and patients treated with thiopurine (12 019·7 U/mL [2·2]; p=0·099), ustekinumab (11 089·3 U/mL [2·8]; p=0·060), or vedolizumab (13 564·9 U/mL [2·4]; p=0·27). In multivariable modelling, lower anti-SARS-CoV-2 S1 RBD antibody concentrations were independently associated with infliximab (geometric mean ratio 0·15 [95% CI 0·11-0·21]; p<0·0001), tofacitinib (0·52 [CI 0·31-0·87]; p=0·012), and thiopurine (0·69 [0·51-0·95]; p=0·021), but not with ustekinumab (0·64 [0·39-1·06]; p=0·083), or vedolizumab (0·84 [0·54-1·30]; p=0·43). Previous SARS-CoV-2 infection (1·58 [1·22-2·05]; p=0·0006) was independently associated with higher anti-SARS-CoV-2 S1 RBD antibody concentrations and older age (0·88 [0·80-0·97]; p=0·0073) was independently associated with lower anti-SARS-CoV-2 S1 RBD antibody concentrations. Antigen-specific T-cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T-cell responses were significantly reduced relative to healthy controls (p=0·021)., Interpretation: A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors., Funding: Pfizer., Competing Interests: Declaration of interests JLA reports sponsorship from Vifor Pharma for accommodation and travel to BSG 2019, outside the submitted work. NAK reports grants from AbbVie, Biogen, Celgene, Celtrion, Galapagos, MSD, Napp, Pfizer, Pharmacosmos, Roche, and Takeda; consulting fees from Amgen, Bristol Myers Squibb, Falk, Janssen, Mylan, Pharmacosmos, Galapagos, Takeda, and Tillotts; personal fees from Allergan, Celltrion, Falk, Ferring, Janssen, Pharmacosmos, Takeda, Tilllotts, and Galapagos; and support for attending meetings from AbbVie, Falk, and Janssen, outside the submitted work. AS has received travel expense support from Janssen. SS reports grants from Takeda, AbbVie, Tillots Pharma, Janssen, Pfizer, and Biogen; and personal fees from Takeda, AbbVie, Janssen, Pharmacocosmos, Biogen, Pfizer, Tillots Pharma, and Falk Pharma, outside the submitted work. ALH reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, Atlantic, Bristol Myers Squibb, Celltrion, Falk, Galapogos, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire, and Takeda; global steering committee for Genentech; support for attending meetings from AbbVie, Takeda, and Janssen; and participation on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Atlantic, Bristol Myers Squibb, Galapogos, Janssen, Pfizer, and Takeda. PMI reports grants and personal fees from Celltrion, Takeda, Pfizer, Galapagos; grants from MSD; and personal fees from Gilead, AbbVie, Janssen, Bristol Myers Squibb, Lilly, and Arena, outside the submitted work. MP receives unrestricted educational grants from Pfizer for genetic analyses to support the IBD BioResource, and speaker fees from Janssen. GRJ has received grants from Wellcome Trust and ECCO; speaker fees from Takeda, Ferring, and Janssen; and support for attending meetings or travel from Ferring. KK reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen and Ferring; support for attending meetings or travel from Janssen and Takeda; and participation on a data safety monitoring board or advisory board for Janssen and Predict Immune. SB reports funding from Ferring and Dr Falk for accommodation, travel, and meeting fees. KVP reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Dr Falk, Janssen, PreddictImmune, and Takeda; support for attending meetings or travel from AbbVie, Ferring, Janssen, and Tillots; and participation on a data safety monitoring board or advisory board for AbbVie, Galapagos, and Janssen. AJK reports consulting fees from Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer and Takeda; support for attending meetings or travel from Janssen, Tillots, and Norgine; and participation on a data safety monitoring board or advisory board for AbbVie. LCH reports support for attending meetings or travel from AbbVie. CWL reports a Future Leaders Fellow award from UKRI; personal consulting fees from Galapagos, AbbVie, Takeda, Pfizer, Janssen, and Iterative Scopes; institutional consulting fees from Trellus Health; personal fees from Galapagos, AbbVie, Takeda, Pfizer, Janssen, GSK, Gilead, Fresnius Kabi, Ferring, and Dr Falk; and support for attending meetings from Galapagos, AbbVie, Takeda, Pfizer, Janssen, GSK, Gilead, Fresnius Kabi, Ferring, and Dr Falk. RJB and DMA are members of the Global T cell Expert Consortium and have consulted for Oxford Immunotec outside the submitted work. JRG reports grants from F Hoffmann-La Roche AG; grants from Biogen, Celltrion Healthcare, and Galapagos NV; and non-financial support from Immundiagnostik, during the conduct of the study. TA reports grant funding from Pfizer to his institution to deliver this study; grants from Celltrion, Roche, Takeda, Biogen, and Galapagos; and honoraria for lectures from Takeda and Roche, outside the submitted work. Financial support for the VIP study was provided as a research grant by Pfizer and NP is the principal investigator on this grant. NP has received research grants from Bristol Myers Squibb outside the submitted work; reports personal fees from Takeda, Janssen, Pfizer, Bristol Myers Squibb, AbbVie, Roche, Lilly, Allergan, and Celgene, outside the submitted work; and has served as a speaker or advisory board member for AbbVie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda, and Vifor Pharma. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Urinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome., Aim: To compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome., Methods: Urine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance ( 1 H NMR) spectroscopy., Results: Microbiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (p = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing., Conclusions: Bowel cleansing causes a temporary disturbance in bacterial alpha diversity measured in faeces, but no significant changes in the faecal and urine metabolic profiles, suggesting that overall the faecal microbiome and its associated metabolome is resistant to the effects of an induced osmotic diarrhoea., (© 2022. The Author(s).)

Background: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs., Methods: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing., Findings: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p<0·0001), infliximab plus thiopurine (111·1 U/mL [5·7]; p<0·0001), or tofacitinib (429·5 U/mL [3·1]; p=0·0012) compared with controls (1578·3 U/mL [3·7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL [4·3]; p=0·74), ustekinumab (582·4 U/mL [4·6]; p=0·11), or vedolizumab (954·0 U/mL [4·1]; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations., Interpretation: For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised., Funding: Pfizer., Competing Interests: Declaration of interests JLA reports sponsorship from Vifor Pharma for accommodation and travel to the British Society of Gastroenterology annual meeting 2019, outside the submitted work. NAK reports grants from AbbVie, Biogen, Celgene, Celtrion, Galapagos, MSD, Napp, Pfizer, Pharmacosmos, Roche, and Takeda; consulting fees from Amgen, Bristol Myers Squibb, Falk, Janssen, Mylan, Pharmacosmos, Galapagos, Takeda, and Tillotts; personal fees from Allergan, Celltrion, Falk, Ferring, Janssen, Pharmacosmos, Takeda, Tilllotts, and Galapagos; and support for attending meetings from AbbVie, Falk, and Janssen, outside the submitted work. AS has received travel expense support from Janssen. SS reports grants from Takeda, AbbVie, Tillots Pharma, Janssen, Pfizer, and Biogen, and personal fees from Takeda, AbbVie, Janssen, Pharmacocosmos, Biogen, Pfizer, Tillots Pharma, and Falk Pharma, outside the submitted work. ALH reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, AZ, Atlantic, Bristol Myers Squibb, Celltrion, Falk, Galapogos, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire, and Takeda; participation on the Global Steering Committee for Genentech; support for attending meetings from AbbVie, Takeda, and Janssen; and participation on a data safety monitoring board or advisory board for AbbVie, AZ, Atlantic, Bristol Myers Squibb, Galapogos, Janssen, Pfizer, and Takeda. PMI reports grants from Celltrion, Takeda, MSD, Pfizer, and Galapagos, and personal fees from Celltrion, Takeda, Pfizer, Galapagos, Gilead, AbbVie, Janssen, Bristol Myers Squibb, Lilly, and Arena, outside the submitted work. MP receives unrestricted educational grants from Pfizer for genetic analyses to support the IBD BioResource and speaker fees from Janssen. GRJ has received grants from the Wellcome Trust and ECCO; speaker fees from Takeda, Ferring, and Janssen; and support for attending meetings or travel from Ferring. KK reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen and Ferring; support for attending meetings or travel from Janssen and Takeda; and participation on a data safety monitoring board or advisory board for Janssen and PredictImmune. KVP reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, DrFalk, Janssen, PreddictImmune, and Takeda; support for attending meetings or travel from AbbVie, Ferring, Janssen, and Tillots; and participation on a data safety monitoring board or advisory board for AbbVie, Galapagos, and Janssen. AJK reports consulting fees from Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer and Takeda; support for attending meetings or travel from Janssen, Tillots, and Norgine; and participation on a data safety monitoring board or advisory board for AbbVie. LCH reports support for attending meetings or travel from AbbVie. CWL reports a Future Leaders Fellow award from UK Research and Innovation; personal consulting fees from Galapagos, AbbVie, Takeda, Pfizer, Janssen, and Iterative Scopes; institutional consulting fees from Trellus Health; personal fees from Galapagos, AbbVie, Takeda, Pfizer, Janssen, GSK, Gilead, Fresnius Kabi, Ferring, and Dr Falk; and support for attending meetings from Galapagos, AbbVie, Takeda, Pfizer, Janssen, GSK, Gilead, Fresnius Kabi, Ferring, and Dr Falk. RJB and DMA are members of the Global T cell Expert Consortium and have consulted for Oxford Immunotec outside the submitted work. JRG reports grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, and Galapagos, and non-financial support from Immundiagnostik, during the conduct of the study. TA reports grant funding from Pfizer to his institution to deliver this study; grants from Celltrion, Roche, Takeda, Biogen, and Galapagos; and honoraria for lectures from Takeda and Roche, outside the submitted work. NP is the principal investigator on the research grant from Pfizer that helped to fund the VIP study; has received research grants from Bristol Myers Squibb outside the submitted work; reports personal fees from Takeda, Janssen, Pfizer, Bristol Myers Squibb, AbbVie, Roche, Lilly, Allergan, and Celgene, outside the submitted work; and has served as a speaker or advisory board member for AbbVie, Allergan, Bristol Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda, and Vifor Pharma. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Soil microbial communities perform vital ecosystem functions, such as the decomposition of organic matter to provide plant nutrition. However, despite the functional importance of soil microorganisms, attribution of ecosystem function to particular constituents of the microbial community has been impeded by a lack of information linking microbial function to community composition and structure. Here, we propose a function-first framework to predict how microbial communities influence ecosystem functions. We first view the microbial community associated with a specific function as a whole and describe the dependence of microbial functions on environmental factors (e.g., the intrinsic temperature dependence of bacterial growth rates). This step defines the aggregate functional response curve of the community. Second, the contribution of the whole community to ecosystem function can be predicted, by combining the functional response curve with current environmental conditions. Functional response curves can then be linked with taxonomic data in order to identify sets of "biomarker" taxa that signal how microbial communities regulate ecosystem functions. Ultimately, such indicator taxa may be used as a diagnostic tool, enabling predictions of ecosystem function from community composition. In this paper, we provide three examples to illustrate the proposed framework, whereby the dependence of bacterial growth on environmental factors, including temperature, pH, and salinity, is defined as the functional response curve used to interlink soil bacterial community structure and function. Applying this framework will make it possible to predict ecosystem functions directly from microbial community composition., (© 2021 The Authors. Ecology published by Wiley Periodicals LLC on behalf of Ecological Society of America.)

Background: The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype., Aims: To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota., Methods: We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included., Results: We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients., Conclusions: Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments., (© 2021 John Wiley & Sons Ltd.)

Fungi and bacteria are the two principal microbial groups in soil, responsible for the breakdown of organic matter (OM). The relative contribution of fungi and bacteria to decomposition is thought to impact biogeochemical cycling at the ecosystem scale, whereby bacterially dominated decomposition supports the fast turnover of easily available substrates, whereas fungal-dominated decomposition leads to the slower turnover of more complex OM. However, empirical support for this is lacking. We used soils from a detritus input and removal treatment experiment in an old-growth coniferous forest, where above- and belowground litter inputs have been manipulated for 20 yr. These manipulations have generated variation in OM quality, as defined by energetic content and proxied as respiration per g soil organic matter (SOM) and the δ 13 C signature in respired CO 2 and microbial PLFAs. Respiration per g SOM reflects the availability and lability of C substrate to microorganisms, and the δ 13 C signature indicates whether the C used by microorganisms is plant derived and higher quality (more δ 13 C depleted) or more microbially processed and lower quality (more δ 13 C enriched). Surprisingly, higher quality C did not disproportionately benefit bacterial decomposers. Both fungal and bacterial growth increased with C quality, with no systematic change in the fungal-to-bacterial growth ratio, reflecting the relative contribution of fungi and bacteria to decomposition. There was also no difference in the quality of C targeted by bacterial and fungal decomposers either for catabolism or anabolism. Interestingly, respired CO 2 was more δ 13 C enriched than soil C, suggesting preferential use of more microbially processed C, despite its lower quality. Gross N mineralization and consumption were also unaffected by differences in the ratio of fungal-to-bacterial growth. However, the ratio of C to gross N mineralization was lower than the average C/N of SOM, meaning that microorganisms specifically targeted N-rich components of OM, indicative of selective microbial N-mining. Consistent with the δ 13 C data, this reinforces evidence for the use of more microbially processed OM with a lower C/N ratio, rather than plant-derived OM. These results challenge the widely held assumption that microorganisms favor high-quality C sources and suggest that there is a trade-off in OM use that may be related to the growth-limiting factor for microorganisms in the ecosystem., (© 2021 The Authors. Ecology published by Wiley Periodicals LLC on behalf of Ecological Society of America.)

Background: There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes., Methods: The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov, NCT04411784., Findings: We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes., Interpretation: The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Climate change is exposing high-latitude systems to warming and a shift towards more shrub-dominated plant communities, resulting in increased leaf-litter inputs at the soil surface, and more labile root-derived organic matter (OM) input in the soil profile. Labile OM can stimulate the mineralization of soil organic matter (SOM); a phenomenon termed "priming." In N-poor subarctic soils, it is hypothesized that microorganisms may "prime" SOM in order to acquire N (microbial N-mining). Increased leaf-litter inputs with a high C/N ratio might further exacerbate microbial N demand, and increase the susceptibility of N-poor soils to N-mining. We investigated the N-control of SOM mineralization by amending soils from climate change-simulation treatments in the subarctic (+1.1°C warming, birch litter addition, willow litter addition, and fungal sporocarp addition) with labile OM either in the form of glucose (labile C; equivalent to 400 µg C/g fresh [fwt] soil) or alanine (labile C + N; equivalent to 400 µg C and 157 µg N/g fwt soil), to simulate rhizosphere inputs. Surprisingly, we found that despite 5 yr of simulated climate change treatments, there were no significant effects of the field-treatments on microbial process rates, community structure or responses to labile OM. Glucose primed the mineralization of both C and N from SOM, but gross mineralization of N was stimulated more than that of C, suggesting that microbial SOM use increased in magnitude and shifted to components richer in N (i.e., selective microbial N-mining). The addition of alanine also resulted in priming of both C and N mineralization, but the N mineralization stimulated by alanine was greater than that stimulated by glucose, indicating strong N-mining even when a source of labile OM including N was supplied. Microbial carbon use efficiency was reduced in response to both labile OM inputs. Overall, these findings suggest that shrub expansion could fundamentally alter biogeochemical cycling in the subarctic, yielding more N available for plant uptake in these N-limited soils, thus driving positive plant-soil feedbacks., (© 2020 The Authors. Ecology published by Wiley Periodicals LLC on behalf of Ecological Society of America.)

Climate change will alter precipitation patterns with consequences for soil C cycling. An understanding of how fluctuating soil moisture affects microbial processes is therefore critical to predict responses to future global change. We investigated how long-term experimental field drought influences microbial tolerance to lower moisture levels ("resistance") and ability to recover when rewetted after drought ("resilience"), using soils from a heathland which had been subjected to experimental precipitation reduction during the summer for 18 years. We tested whether drought could induce increased resistance, resilience, and changes in the balance between respiration and bacterial growth during perturbation events, by following a two-tiered approach. We first evaluated the effects of the long-term summer drought on microbial community functioning to drought and drying-rewetting (D/RW), and second tested the ability to alter resistance and resilience through additional perturbation cycles. A history of summer drought in the field selected for increased resilience but not resistance, suggesting that rewetting after drought, rather than low moisture levels during drought, was the selective pressure shaping the microbial community functions. Laboratory D/RW cycles also selected for communities with a higher resilience rather than increased resistance. The ratio of respiration to bacterial growth during D/RW perturbation was lower for the field drought-exposed communities and decreased for both field treatments during the D/RW cycles. This suggests that cycles of D/RW also structure microbial communities to respond quickly and efficiently to rewetting after drought. Our findings imply that microbial communities can adapt to changing climatic conditions and that this might slow the rate of soil C loss predicted to be induced by future cyclic drought., (© 2018 John Wiley & Sons Ltd.)

Background and Aims: Distinguishing between the inflammatory bowel diseases [IBD], Crohn's disease [CD] and ulcerative colitis [UC], is important for determining management and prognosis. Selected ion flow tube mass spectrometry [SIFT-MS] may be used to analyse volatile organic compounds [VOCs] in exhaled breath: these may be altered in disease states, and distinguishing breath VOC profiles can be identified. The aim of this pilot study was to identify, quantify, and analyse VOCs present in the breath of IBD patients and controls, potentially providing insights into disease pathogenesis and complementing current diagnostic algorithms., Methods: SIFT-MS breath profiling of 56 individuals [20 UC, 18 CD, and 18 healthy controls] was undertaken. Multivariate analysis included principal components analysis and partial least squares discriminant analysis with orthogonal signal correction [OSC-PLS-DA]. Receiver operating characteristic [ROC] analysis was performed for each comparative analysis using statistically significant VOCs., Results: OSC-PLS-DA modelling was able to distinguish both CD and UC from healthy controls and from one other with good sensitivity and specificity. ROC analysis using combinations of statistically significant VOCs [dimethyl sulphide, hydrogen sulphide, hydrogen cyanide, ammonia, butanal, and nonanal] gave integrated areas under the curve of 0.86 [CD vs healthy controls], 0.74 [UC vs healthy controls], and 0.83 [CD vs UC]., Conclusions: Exhaled breath VOC profiling was able to distinguish IBD patients from controls, as well as to separate UC from CD, using both multivariate and univariate statistical techniques., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Metabonomic techniques have considerable potential in the field of clinical diagnostics, typifying the application of a translational research paradigm. Care must be taken at all stages to apply appropriate methodology with accurate patient selection and profiling, and rigorous data acquisition and handling, to ensure clinical validity.An ever-increasing number of publications in a wide range of diseases and diverse patient groups suggest a variety of potential clinical uses; prospective studies in large validation cohorts are required to bring metabonomics into routine clinical practice. In this chapter, the utility of metabonomics as a diagnostic tool will be discussed.