Fergus Shanahan

University College Cork | UCC · Alimentary Pharmabiotic Centre

Variations in the normal gut microbiome and the existence of context-dependent disease associations have confounded the identification of microbiome markers of health. A reliable indexing of taxa based on their association with host health and microbiome resilience could accelerate development of microbiome-based therapeutics including selection of...

Introduction The chronic inflammatory skin disease Hidradenitis suppurativa (HS) is strongly associated with Crohn’s Disease (CD). HS and CD share clinical similarities and similar inflammatory pathways are upregulated in both conditions. Increased prevalence of inflammatory disease in industrialised nations has been linked to the Western diet. How...

Most of the variance in the human microbiome remains unexplained. Although an extensive list of individual lifestyles shaping the microbiome has been identified, important gaps in knowledge persist. Most human microbiome data are from individuals living in socioeconomically developed countries. This may have skewed the interpretation of microbiome...

Viruses are increasingly recognised as important components of the human microbiome, fulfilling numerous ecological roles including bacterial predation, immune stimulation, genetic diversification, horizontal gene transfer, microbial interactions, and augmentation of metabolic functions. However, our current view of the human gut virome is tainted...

Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesized that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive Escherichia coli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation...

Environmental factors, including westernised diets and alterations to the gut microbiota, are considered risk factors for inflammatory bowel diseases (IBD). The mechanisms underpinning diet-microbiota-host interactions are poorly understood in IBD. We present evidence that feeding a lard-based high-fat (HF) diet can protect mice from developing DSS...

The microbiome contributes to human development and maturation, and is essential for maintenance of health and prevention of disease. While the human genome encodes one’s identity, the microbiome – also individually unique – provides a window on one’s lifestyle and exposure to environmental variables. The microbiome thus serves as a biomarker of ho...

The gut microbiome is a modifier of disease risk because it interacts with nutrition, metabolism, immunity and infection. Aging-related health loss has been correlated with transition to different microbiome states. Microbiome summary indices including alpha diversity are apparently useful to describe these states but belie taxonomic differences th...

In view of the increasing evidence that commonly prescribed, non-antibiotic drugs interact with the gut microbiome, we re-examined the microbiota variance in inflammatory bowel disease (IBD) to determine the degree to which medication and supplement intake might account for compositional differences between disease subtypes and geographic location....

DNA sensor pathways can initiate inflammasome, cell death and type I interferon (IFN) signalling in immune-mediated inflammatory diseases (IMIDs); including type I interferonopathies. We investigated the involvement of these pathways in the pathogenesis of ulcerative colitis (UC); by analysing expression of DNA sensor, inflammasome, and type I IFN...

Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesise that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive Escherichia coli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation....

The colonic microbiome has been implicated in the pathogenesis of colorectal cancer (CRC) and intestinal microbiome alterations are not confined to the tumour. Since data on whether the microbiome normalises or remains altered after resection of CRC are conflicting, we studied the colonic microbiota of patients after resection of CRC. We profiled t...

The gut microbiome is a contributory factor in ageing-related health loss and in several non-communicable diseases in all age groups. Some age-linked and disease-linked compositional and functional changes overlap, while others are distinct. In this Review, we explore targeted studies of the gut microbiome of older individuals and general cohort st...

Background and aims: Computed tomography (CT), often more accessible than magnetic resonance imaging (MRI), remains widely used though radiation exposure is an obvious disadvantage. We previously showed that modern CT technology can achieve over 70% reduction in radiation-dose without loss of accuracy. Here, we compare low- versus conventional-dose...

Rewiring of host cytokine networks is a key feature of inflammatory bowel diseases (IBD) such as Crohn’s disease (CD). Th1-type cytokines—IFN-γ and TNF-α—occupy critical nodes within these networks and both are associated with disruption of gut epithelial barrier function. This may be due to their ability to synergistically trigger the death of int...

Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain-gut interactions, but their role in microbiota-neuro-immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local a...

Carcinoembryogenic antigen cellular adhesion molecules (CEACAMs) are intercellular adhesion molecules highly expressed in intestinal epithelial cells. CEACAM1, -3, -5, -6, -7 are altered in patients suffering from colon cancer and inflammatory bowel diseases (IBD), but their role in the onset and pathogenesis of IBD is not well known. Herein, we ai...

Patients with colorectal cancer (CRC) harbor gut microbiomes that differ in structure and function from those of healthy individuals, suggesting this altered microbiome could contribute to tumorigenesis. Despite increasing evidence implicating the gut microbiome in CRC, the collective role of different microbial consortia in CRC carcinogenesis is u...

Background Treatment with Ivacaftor provides a significant clinical benefit in people with cystic fibrosis (PWCF) with the class III G551D-CFTR mutation. This study determined the effect of CFTR modulation with ivacaftor on the lung microbiota in PWCF. Methods Using both extended-culture and culture-independent molecular methods, we analysed the l...

Purpose Clostridium difficile has been reported to occur in the gastrointestinal tract of 50% of Cystic Fibrosis (CF) subjects, however, clinical C. difficile infection (CDI) is a rare occurrence in this cohort despite the presence of toxigenic and hypervirulent ribotypes. Here, we present the first longitudinal, multicentre analysis of C. difficil...

Irritable Bowel Syndrome (IBS), the most common gastrointestinal disorder, is diagnosed solely on symptoms. Potentially diagnostic alterations in the bacterial component of the gut microbiome (the bacteriome) are associated with IBS, but despite the known role of the virome (particularly bacteriophages), in shaping the gut bacteriome, few studies h...

The athlete gut microbiome differs from that of non‐athletes in its composition and metabolic function. Short‐term fitness improvement in sedentary adults does not replicate the microbiome characteristics of athletes. The objective of this study was to investigate whether sustained fitness improvement leads to pronounced alterations in the gut micr...

Background: Prophylactic strategies are urgently needed for prevention of severe inflammatory responses to respiratory viral infections. Bacterial-host interactions may modify the immune response to viral infections. Methods: We examined the contribution of Intranasal administration of two different Bifidobacterium longum strains or its isolated...

Modern lifestyles increase the risk of chronic diseases, in part by modifying the microbiome, but the health effects of lifestyles enforced on ethnic minorities are understudied1–3. Lifestyle affects the microbiome early in life, when the microbiome is assembled and the immune system is undergoing maturation4–6. Moreover, the influence of lifestyle...

Objective The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. Design Here, we rank the size effect of disease activity, medications, diet and geographic location of the fae...

Objective: The composition and metabolic function of the gut microbiome in the elite athlete differs from that of non-athletes. However, short-term fitness improvement in the sedentary adult does not replicate the microbiome characteristics seen in the athlete. Whether sustained fitness improvement over a prolonged period can lead to pronounced and...

Background & Aims Impaired attention and response inhibition has been reported in patients with Crohn’s disease (CD) in clinical remission. Prospective studies are needed to determine whether this is a stable feature of CD and whether a similar impairment is evident in ulcerative colitis (UC). Thus, our aims were to examine whether patients with CD...

Proteins of the BCL-2 family are evolutionarily conserved modulators of apoptosis that function as sensors of cellular integrity. Over the past three decades multiple BCL-2 family members have been identified, many of which are now fully incorporated into regulatory networks governing the mitochondrial apoptotic pathway. For some, however, an exact...

Introduction. Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. Aim. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. Methodology. Ex vivo f...

Background & aims: Irritable bowel syndrome (IBS) is a heterogeneous disorder but diagnoses and determination of sub-types are made based on symptoms. We profiled fecal microbiomes of patients with and without irritable bowel syndrome (IBS) to identify biomarkers of this disorder. Methods: We collected fecal and urine samples from 80 patients wi...

Microbial colonization of the gastrointestinal tract plays a crucial role in the development of enteric and central nervous system functionality. The serotonergic system has been heavily implicated in microbiota-gut-brain axis signaling, particularly in proof-of-principle studies in germ-free (GF) animals. One aspect of the serotonergic system that...

Objective: To investigate compositional differences in the gut microbiota associated with bone homeostasis and fractures in a cohort of older adults. Methods: Faecal microbiota profiles were determined from 181 individuals with osteopenia (n = 61) or osteoporosis (n = 60), and an age- and gender-matched group with normal BMD (n = 60). Analysis o...

The gut microbiome is a community of microbes residing within the gastrointestinal tract with the potential to significantly influence host health. This infographic summarises the key features of a healthy gut microbiome, highlights its role in athlete health and performance, and identifies its positive and negative influences. This information wil...

Objectives: Compositional and functional adaptions occur in the gut microbiome in response to habitual physical activity. The response of the gut microbiome to sustained, intense exercise in previously active individuals, however, is unknown. This study aimed to prospectively explore the gut microbiome response of four well-trained male athletes t...

Background Overweight and metabolic problems now add to the burden of illness in patients with Inflammatory Bowel Disease. We aimed to determine if a program of aerobic and resistance exercise could safely achieve body composition changes in patients with Inflammatory Bowel Disease. Methods A randomized, cross-over trial of eight weeks combined ae...

Development of the human gut microbiota commences at birth, with certain bifidobacterial species representing dominant and early colonizers of the newborn gastrointestinal tract. The molecular basis of Bifidobacterium colonization, persistence and presumed communication with the host has remained obscure. We previously identified tight adherence (T...

Objectives Performance of a modified abdominopelvic CT protocol reconstructed using full iterative reconstruction (IR) was assessed for imaging patients presenting with acute abdominal symptoms. Materials and methods Fifty-seven patients (17 male, 40 female; mean age of 56.5 ± 8 years) were prospectively studied. Low-dose (LD) and conventional-dos...

Background: Alteration of the gut microbiota by repeated antibiotic treatment increases susceptibility to Clostridioides difficile infection. Faecal microbiota transplantation from donors with a normal microbiota effectively treats C. difficile infection. Methods: The study involved 10 patients with recurrent C. difficile infection, nine of whom...

Ex vivo colon fermentation systems are highly versatile as models for analyzing gastrointestinal tract microbiota composition and functionality. Ex vivo colon models range in size and functionality from bench-top micro fermenters to large units housed in individualized cabinets. The length of set-up time (including stabilization periods) for each f...

The non-digestible oligosaccharide fraction of maternal milk represents an important of carbohydrate and energy source for saccharolytic bifidobacteria in the gastrointestinal tract during early life. However, not all neonatal bifidobacteria isolates can directly metabolise the complex sialylated, fucosylated, sulphated and/or N-acetylglucosamine-c...

While bile acids (BAs) have long established roles as digestive molecules, recent research also recognises the importance of the role they play in signalling processes. Indeed, they have been found to influence a variety of metabolic activities important for maintaining host health that include potent antimicrobial properties affecting the gut micr...

ELife digest In our bodies, there are at least as many microbial cells as human cells. These microbes, known collectively as the microbiome, influence the activity of our brain and also our behaviour. Studies in species from insects to primates have shown that the microbiome affects social behaviour in particular. For example, germ-free mice, which...

Functional enrichment DSGs

Differentially expressed genes

Functional enrichment DEGs

Details on RNA sample quality and sequencing quality control

Correlation gene expression with behaviour

Raw FastQC quality control files for sequencing data

The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate uniqu...

In a recent study1 we reported that tissue-associated microbial Co-abundance Groups (CAGs) were differentially associated with CRC. Two of the CAGs, which we named Pathogen CAG and Prevotella CAG, were correlated with a gene expression signature indicative of a TH17 response. A TH17 response has been associated with decreased survival in patients w...

Background and aims Microbiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screen...

Background: Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at Cork CF Centre is 23%. This study assessed the impact of CFTR modulation on multiple modalities of patient assessment. Methods: Thirty three patients with the G551D mutation were assessed at ba...

Background: There is growing evidence for a role of the gut microbiome in shaping behaviour relevant to many psychiatric and neurological disorders. Preclinical studies using germ-free (GF) animals have been essential in contributing to our current understanding of the potential importance of the host microbiome for neurodevelopment and behaviour....