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ABSTRACTInteractions between diet and gastrointestinal microbiota influence health status and outcomes. Evaluating these relationships requires accurate quantification of dietary variables relevant to microbial metabolism, however current dietary assessment methods focus on dietary components relevant to human digestion only. The aim of this study was to synthesize research on foods and nutrients that influence human gut microbiota and thereby identify knowledge gaps to inform dietary assessment advancements toward better understanding of diet–microbiota interactions. Thirty-eight systematic reviews and 106 primary studies reported on human diet-microbiota associations. Dietary factors altering colonic microbiota included dietary patterns, macronutrients, micronutrients, bioactive compounds, and food additives. Reported diet-microbiota associations were dominated by routinely analyzed nutrients, which are absorbed from the small intestine but analyzed for correlation to stool microbiota. Dietary derived microbiota-relevant nutrients are more challenging to quantify and underrepresented in included studies. This evidence synthesis highlights advancements needed, including opportunities for expansion of food composition databases to include microbiota-relevant data, particularly for human intervention studies. These advances in dietary assessment methodology will facilitate translation of microbiota-specific nutrition therapy to practice.

Abstract The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.

Abstract Background Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment. Main body This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents. Conclusion Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.

Introduction Multiple cohort studies have been established to investigate the impact of early life factors on development and health outcomes. In Australia the majority of these studies were established more than 20 years ago and, although longitudinal in nature, are inherently susceptible to socioeconomic, environmental and cultural influences which change over time. Additionally, rapid leaps in technology have increased our understanding of the complex role of gene–environment interactions in life course health, highlighting the need for new cohort studies with repeated biological sampling and in-depth phenotype data across the first 1000 days of life from conception.Methods and analysis The Newcastle 1000 (NEW1000) Study, based in the regional city of Newcastle, New South Wales, was developed after an extensive consultation process involving 3 years of discussion with key stakeholders and healthcare consumer organisations and seven healthcare consumer workshops. This prospective population-based pregnancy cohort study will recruit 500 families per year for 5 years, providing detailed, longitudinal, multisystem phenotyping, repeated ultrasound measures and serial sample collection to investigate healthcare consumer identified health outcomes of priority. Stage 1 will involve recruitment of pregnant participants and their partners at 14 weeks gestation, with dense phenotype data and biological samples collected at 14, 20, 28 and 36 weeks gestation and serial ultrasound measures at 20, 28, 36 and 40 weeks, with postpartum follow-up at 6 weeks and 6 months. Biological samples will be used for biomarker discovery and sequencing of the genome, transcriptome, epigenome, microbiome and metabolome.Ethics and dissemination Ethics approval was obtained from Hunter New England Local Health District Ethics Committee (2020/ETH02881). Outcomes will be published in peer-reviewed journals, disseminated to participants through the NEW1000 website, presented at scientific conferences, and written reports to local, state and national government bodies and key stakeholders in the healthcare system to inform policy and evidence-based practice.

Abstract Background Irritable bowel syndrome (IBS) is considered a disorder of gut-brain interaction (DGBI), presenting as chronic abdominal pain and altered defaecation. Symptoms are often food related. Much work in the field has focused on identifying physiological, immune and microbial abnormalities in the colon of patients; however, evidence of small intestinal immune activation and microbial imbalance has been reported in small studies. The significance of such findings has been largely underappreciated despite a growing body of work implicating small intestinal homeostatic imbalance in the pathogenesis of DGBIs. Main text Small intestinal mechanosensation is a characteristic feature of IBS. Furthermore, altered small intestinal barrier functions have been demonstrated in IBS patients with the diarrhoea-predominant subtype. Small intestinal bacterial overgrowth and increased populations of small intestinal mast cells are frequently associated with IBS, implicating microbial imbalance and low-grade inflammation in the pathogenesis of IBS. Furthermore, reports of localised food hypersensitivity responses in IBS patients implicate the small intestine as the site of immune-microbial-food interactions. Conclusions Given the association of IBS symptoms with food intake in a large proportion of patients and the emerging evidence of immune activation in these patients, the current literature suggests the pathogenesis of IBS is not limited to the colon but rather may involve dysfunction of the entire intestinal tract. It remains unclear if regional variation in IBS pathology explains the various symptom phenotypes and further work should consider the intestinal tract as a whole to answer this question.

BackgroundFunctional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD.ObjectiveThis study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology.MethodsWe identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls.ResultsThere was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, p=0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p=0.027) subsets. Peripheral T cell populations were unchanged between FD and control.ConclusionOur findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.

Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function, psychiatric comorbidities, gut-homing immune cells, and duodenal mucosa-associated microbiome (d-MAM) in FGID patients and controls with and without self-reported wheat sensitivity (SR-NCWS). We recruited 40 FGID patients and 20 controls referred by GPs for treatment. Gastrointestinal/extraintestinal symptoms, visceral sensory function, psychological comorbidities, and SR-NCWS were assessed in a standardized approach. Peripheral gut homing T-cells (CD4+α4+β7+CCR9+/CD8+α4+β7+CCR9+) were quantified, and the d-MAM was assessed by DNA sequencing for 46 subjects. Factors of bacterial genera were extracted utilizing factor analysis with varimax rotation and factors univariately associated with FGID or SR-NCWS included in a subsequent multivariate analysis of variance to identify statistically independent discriminators. Anxiety scores (p

Abstract In this study, the intestinal permeability of metal(loid)s (MLs) such as arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) was examined, as influenced by gut microbes and chelating agents using an in vitro gastrointestinal/Caco-2 cell intestinal epithelium model. The results showed that in the presence of gut microbes or chelating agents, there was a significant decrease in the permeability of MLs (As-7.5%, Cd-6.3%, Pb-7.9% and Hg-8.2%) as measured by apparent permeability coefficient value (P app), with differences in ML retention and complexation amongst the chelants and the gut microbes. The decrease in ML permeability varied amongst the MLs. Chelating agents reduce intestinal absorption of MLs by forming complexes thereby making them less permeable. In the case of gut bacteria, the decrease in the intestinal permeability of MLs may be associated to a direct protection of the intestinal barrier against the MLs or indirect intestinal ML sequestration by the gut bacteria through adsorption on bacterial surface. Thus, both gut microbes and chelating agents can be used to decrease the intestinal permeability of MLs, thereby mitigating their toxicity.

Functional dyspepsia (FD) is a highly prevalent disorder of gut-brain interaction (DGBI), previously known as a functional gastrointestinal disorder. Characterized by early satiety, postprandial fullness, and/or epigastric pain or burning, diagnosis depends on positive symptomatology and exclusion of obvious structural diseases. A subtle inflammatory phenotype has been identified in FD patients, involving an increase in duodenal mucosal eosinophils, and imbalances in the duodenal gut microbiota. A dysregulated epithelial barrier has also been well described in FD and is thought to be a contributing factor to the low-grade duodenal inflammation observed, however the mechanisms underpinning this are poorly understood. One possible explanation is that alterations in the microbiota and increased immune cells can result in the activation of cellular stress response pathways to perpetuate epithelial barrier dysregulation. One such cellular response pathway involves the stabilization of hypoxia-inducible factors (HIF). HIF, a transcriptional protein involved in the cellular recognition and adaptation to hypoxia, has been identified as a critical component of various pathologies, from cancer to inflammatory bowel disease (IBD). While the contribution of HIF to subtle inflammation, such as that seen in FD, is unknown, HIF has been shown to have roles in regulating the inflammatory response, particularly the recruitment of eosinophils, as well as maintaining epithelial barrier structure and function. As such, we aim to review our present understanding of the involvement of eosinophils, barrier dysfunction, and the changes to the gut microbiota including the potential pathways and mechanisms of HIF in FD. A combination of PubMed searches using the Mesh terms functional dyspepsia, functional gastrointestinal disorders, disorders of gut-brain interaction, duodenal eosinophilia, barrier dysfunction, gut microbiota, gut dysbiosis, low-grade duodenal inflammation, hypoxia-inducible factors (or HIF), and/or intestinal inflammation were undertaken in the writing of this narrative review to ensure relevant literature was included. Given the findings from various sources of literature, we propose a novel hypothesis involving a potential role for HIF in the pathophysiological mechanisms underlying FD.

Circadian rhythms are cyclic patterns of physiological, behavioural and molecular events that occur over a 24-h period. They are controlled by the suprachiasmatic nucleus (SCN), the brain’s master pacemaker which governs peripheral clocks and melatonin release. While circadian systems are endogenous, there are external factors that synchronise the SCN to the ambient environment including light/dark cycles, fasting/fed state, temperature and physical activity. Circadian rhythms also provide internal temporal organisation which ensures that any internal changes that take place are centrally coordinated. Melatonin synchronises peripheral clocks to the external time and circadian rhythms are regulated by gene expression to control physiological function. Synchronisation of the circadian system with the external environment is vital for the health and survival of an organism and as circadian rhythms play a pivotal role in regulating GI physiology, disruption may lead to gastrointestinal (GI) dysfunction. Disorders of gut-brain interactions (DGBIs), also known as functional gastrointestinal disorders (FGIDs), are a group of diseases where patients experience reoccurring gastrointestinal symptoms which cannot be explained by obvious structural abnormalities and include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Food timing impacts on the production of melatonin and given the correlation between food intake and symptom onset reported by patients with DGBIs, chronodisruption may be a feature of these conditions. Recent advances in immunology implicate circadian rhythms in the regulation of immune responses, and DGBI patients report fatigue and disordered sleep, suggesting circadian disruption. Further, melatonin treatment has been demonstrated to improve symptom burden in IBS patients, however, the mechanisms underlying this efficacy are unclear. Given the influence of circadian rhythms on gastrointestinal physiology and the immune system, modulation of these rhythms may be a potential therapeutic option for reducing symptom burden in these patients.

Background and aim Inflammatory bowel disease (IBD) refers to a group of complex and chronic conditions that requires long‐term care delivered by a group of healthcare professionals through a multidisciplinary care model. We conducted a systematic review to examine and understand the role of healthcare professionals in the primary care management of IBD, and identify the gaps in IBD management that could be filled by primary care providers such as general practitioners (GPs) and pharmacists. Methods The search strategy retrieved published studies from five databases, and eligible articles were assessed for quality. A gray literature search of the websites of organizations was also undertaken. Results Twenty‐one studies were included, of which 19 were peer‐reviewed research articles and two reports were from organizational bodies. Although studies have shown the roles of GPs, pharmacists, dietitians, and psychologists in IBD management, nurses and gastroenterologists were the key drivers delivering specialized care to IBD patients. Many key services are accessible only for hospital inpatients (tertiary care) or through outpatient clinics (secondary care) with an absence of a multidisciplinary approach including GPs and pharmacists. Conclusion Gastroenterologists and nurses have an important role in the delivery of care to patients with chronic gastrointestinal diseases including IBD, coeliac disease, irritable bowel syndrome, and functional dyspepsia. The role of nurses includes provision of specialized care to IBD patients, as well as supportive care such as education, monitoring of therapy, and ongoing assistance. The available evidence shows many opportunities for primary care providers to play a more active role in the management of IBD patients.

Background: Colorectal cancer is the third most common cancer worldwide. Almost half of those that have a potentially curative resection go on to develop metastatic disease. A recognized risk for recurrence is perioperative systemic inflammation and sepsis. Neutrophil extracellular traps have been implicated as promotors of tumor progression. We aimed to examine the evidence in the literature for an association between neutrophil extracellular traps and postoperative metastasis in colorectal cancer. Materials and methods: Studies published between 2000 and December 2018 that examined the role of neutrophil extracellular traps in sepsis and inflammation in colorectal cancer and in relation to tumor-related outcomes were identified through a database search of Cochrane, CINAHL, and MEDLINE. Quality and bias assessment was carried out by 2 reviewers. Results: Of 8,940 screened and of the 30 studies included, 21 were observational, 5 were in vivo experimental, 1 was in vitro, and 3 used a combination of these approaches. Conclusion: There is clear evidence from the literature that presence of a preoperative systemic inflammatory response predicts cancer recurrence following potentially curative resection, but the evidence for association of sepsis and progression is lacking. There is robust experimental evidence in murine models showing that neutrophil extracellular traps are present in sepsis and are associated with cancer progression. Some human observational studies corroborate the prognostic significance of neutrophil extracellular traps in progression of colorectal cancer. Further human studies are needed to translate the experimental evidence and to definitively associate sepsis and neutrophil extracellular traps with poor colorectal cancer-specific outcomes.

Incidence rates of inflammatory bowel disease (IBD) are increasing worldwide. This correlates with increased consumption of red meats, alcohol, refined sugars, oils and animal fats, typical of a “Western” diet. Poor dietary habits are the most ubiquitous environmental factor implicated in IBD, along with gastrointestinal dysbiosis. Taste genetics and oral receptor expression levels determine dietary preferences and therefore, nutritional intake. Taste receptors (TRs) are also expressed throughout the gastrointestinal tract, where they are involved in modulating metabolic processes and gastrointestinal function. Importantly, these receptors are known to be involved in the modulation of inflammatory processes in the respiratory tract. In this system, TRs detect and respond to bacteria and bacterial signalling molecules and initiate protective responses. We propose that TRs play a similar role in the gastrointestinal tract, thereby modulating risk for IBD. TRs may indirectly affect risk for IBD by altering dietary intake, and therefore microbial composition and function. Alternatively, TRs may directly detect and respond to gastrointestinal bacterial components. Overall, there is evidence to suggest an emerging role for TRs in the aetiology of IBD. Furthermore, targeting these receptors via dietary modulation may have therapeutic potential. Keywords: Taste receptors, Nutrition, Microbiome, Inflammatory bowel disease, Diet

Functional dyspepsia (FD) is a common disorder of gut-brain interaction, characterised by upper gastrointestinal symptom profiles that differentiate FD from the irritable bowel syndrome (IBS), although the two conditions often co-exist. Despite food and eating being implicated in FD symptom induction, evidence-based guidance for dietetic management of FD is limited. The aim of this narrative review is to collate the possible mechanisms for eating-induced and food-related symptoms of FD for stratification of dietetic management. Specific carbohydrates, proteins and fats, or foods high in these macronutrients have all been reported as influencing FD symptom induction, with removal of ‘trigger’ foods or nutrients shown to alleviate symptoms. Food additives and natural food chemicals have also been implicated, but there is a lack of convincing evidence. Emerging evidence suggests the gastrointestinal microbiota is the primary interface between food and symptom induction in FD, and is therefore a research direction that warrants substantial attention. Objective markers of FD, along with more sensitive and specific dietary assessment tools will contribute to progressing towards evidence-based dietetic management of FD.

Globally, more than one-third of adults are overweight. Overweight and obesity are complex and multifaceted conditions, associated with an increased risk of chronic illness and early mortality. While there are known risk factors, these alone do not fully explain the varying outcomes between individuals. Recently, taste receptors have been proposed to have a role in the risk for obesity. These receptors are expressed throughout the gastrointestinal tract. In this system, they may be involved in modulating dietary intake and metabolic processes. The taste 2 family of receptors (T2Rs) detects bitter compounds. Receptors T2R4 and T2R5 detect (-)-epicatechin (epicatechin), an antioxidant polyphenol, which may have protective effects against obesity. However, the potential role for taste receptors in this association has not been explored. This study assessed whether polymorphisms in TAS2R4 (rs2233998 and rs2234001) and TAS2R5 (rs2227264) were associated with body mass index (BMI). Genotyping (Taqman qPCR assays) was performed on DNA extracted from blood samples (n = 563) from an elderly cohort. Homozygosity for the minor allele of all polymorphisms was significantly associated with a lower BMI in males. The TAS2R4-rs2233998 CC genotype, the TAS2R4-rs2234001 CC genotype and the TAS2R5-rs2227264 TT genotype were associated with lower BMI (2.1, 2.1 and 2.2 units; p = 0.002, 0.003 and 0.001, respectively). Epicatechin intake was not associated with BMI and genotype was not associated with epicatechin intake. This suggests that the association between TAS2R genotype and elevated BMI risk occurs through altered extra-oral responses and not directly via altered epicatechin intake.

Background and aims: Chronic disease, particularly inflammatory bowel disease (IBD), requires a multifaceted approach to managing patients, but it is apparent that primary care pharmacists are being underutilized. To demonstrate the benefits of pharmacist interventions in primary care, a systematic review was conducted of interventions in asthma and type 2 diabetes where pharmacists have a defined role in chronic disease management. We also explored potential opportunities for primary care pharmacists to deliver tailored care to patients with inflammatory bowel disease. Methods: The search strategy retrieved original research articles from seven databases; eligible articles were assessed for inclusion. Quality appraisal was performed independently by two reviewers. Results: Thirty-seven included studies were grouped into four categories of interventions: education/counseling (43%), medication management (34%), monitoring/follow-up (17%), and screening/risk prevention (6%). Education plus counseling was reported as the main intervention delivered by pharmacists. Three measurable outcomes were identified: clinical, humanistic (e.g., quality of life), and economic. Clinical outcomes (63%) were reported more commonly than humanistic (26%) and economic (11%) outcomes. Pharmacist interventions led to statistically significant improvements in control of disease, severity, and medication adherence, as well as improvements in overall patient satisfaction, quality of life among patients with asthma and type 2 diabetes. Conclusion: As one of the most accessible sources of primary health care, pharmacists are well-placed to minimize the impact of chronic diseases on patients and communities. Evidence suggests there are opportunities for primary care pharmacists to play a more active role in the management of chronic diseases such as IBD.

Introduction: Functional dyspepsia (FD), characterised by symptoms of epigastric pain or early satiety and post prandial distress, has been associated with duodenal eosinophilia, raising the possibility that it is driven by an environmental allergen. Non-coeliac gluten or wheat sensitivity (NCG/WS) has also been associated with both dyspeptic symptoms and duodenal eosinophilia, suggesting an overlap between these two conditions. The aim of this study was to evaluate the role of wheat (specifically gluten and fructans) in symptom reduction in participants with FD in a pilot randomized double-blind, placebo controlled, dietary crossover trial. Methods: Patients with Rome III criteria FD were recruited from a single tertiary centre in Newcastle, Australia. All were individually counselled on a diet low in both gluten and fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) by a clinical dietitian, which was followed for four weeks (elimination diet phase). Those who had a ≥30% response to the run-in diet, as measured by the Nepean Dyspepsia Index, were then re-challenged with ‘muesli’ bars containing either gluten, fructan, or placebo in randomised order. Those with symptoms which significantly reduced during the elimination diet, but reliably reappeared (a mean change in overall dyspeptic symptoms of ≥30%) with gluten or fructan re-challenge were deemed to have wheat induced FD. Results: Eleven participants were enrolled in the study (75% female, mean age 43 years). Of the initial cohort, nine participants completed the elimination diet phase of whom four qualified for the rechallenge phase. The gluten-free, low FODMAP diet led to an overall (albeit non-significant) improvement in symptoms of functional dyspepsia in the diet elimination phase (mean NDI symptom score 71.2 vs. 47.1, p = 0.087). A specific food trigger could not be reliably demonstrated. Conclusions: Although a gluten-free, low-FODMAP diet led to a modest overall reduction in symptoms in this cohort of FD patients, a specific trigger could not be identified. The modified Salerno criteria for NCG/WS identification trialled in this dietary rechallenge protocol was fit-for-purpose. However, larger trials are required to determine whether particular components of wheat induce symptoms in functional dyspepsia.

Background and aim: Managing patients with a chronic condition such as inflammatory bowel disease (IBD), requires a multidiscipline approach. The pharmacist might be the first point of contact for patients with initial symptoms or relapsing flares, yet there is no available literature on the role of pharmacists in IBD management. We conducted a survey to explore pharmacists’ confidence in and potential barriers to managing IBD and assess the impact of IBD education on their confidence in IBD management. Methods: Surveys assessing confidence levels in managing IBD, additional learning opportunities about IBD and barriers to their learning of IBD management were provided to pharmacists for completion before and after attending an IBD-specific education session at a national conference. Results: Of the 195 attendees, 125 participants completed the survey (64%). Most respondents reported a low to mid-range level of confidence with managing IBD. Specifically, they were only slightly confident in decision making on patient care, addressing patient needs and providing additional support for IBD patients; and somewhat confident with understanding, management and providing relevant information on IBD. Whist the education session improved pharmacists perceived level of confidence, most respondents indicated a need to learn more about IBD. Areas of additional learning included science, drug therapy, treatments (includes non-pharmacological options as well) and guidelines. A majority of pharmacists identified time constraints as a key barrier to learning. Conclusion: Pharmacists lack sufficient confidence about managing inflammatory bowel disease. These data indicate support within the pharmacy profession to play a more active role in the management of IBD.

Food ingestion is heavily implicated in inducing symptoms of irritable bowel syndrome (IBS) and functional dyspepsia (FD), which affect over one-third of adults in developed countries. The primary aim of this paper was to assess the alignment of dietary assessment and symptom-reporting capture periods in diet-related studies on IBS or FD in adults. Secondary aims were to compare the degree of alignment, validity of symptom-reporting tools and reported significant associations between food ingestion and symptoms. A five-database systematic literature search resulted in 40 included studies, from which data were extracted and collated. The food/diet and symptom capture periods matched exactly in 60% (n = 24/40) of studies, overlapped in 30% (n = 12/40) of studies and were not aligned in 10% (n = 4/40) of studies. Only 30% (n = 12/40) of studies that reported a significant association between food and global gastrointestinal symptoms used a validated symptom-reporting tool. Of the thirty (75%) studies that reported at least one significant association between individual gastrointestinal symptoms and dietary intake, only four (13%) used a validated symptom tool. Guidelines to ensure that validated symptom-reporting tools are matched with fit-for-purpose dietary assessment methods are needed to minimise discrepancies in the alignment of food and symptom tools, in order to progress functional gastrointestinal disorder research.

The type 2 family of taste receptors (T2Rs) detect and respond to bitter tastants. These receptors are expressed throughout the gastrointestinal (GI) tract, with location dependant roles. In the oral cavity, T2Rs are involved in the conscious perception of bitter tastants, while in the lower GI tract they have roles in chemoreception and regulation of GI function. Through these diverse roles, these receptors may be involved in modulating appetite and diet, with consequences for weight regulation and obesity. Interestingly, the concentration of T2Rs in the GI tract is greatest in the large intestine, the organ with the densest colonisation of bacteria. The gut microbiome has been the subject of intense research, as a plethora of roles linking microbiota to human health continue to be uncovered. Of particular interest is the microbial signature associated with obesity. Obesity is a leading health concern, and advances in our understanding of this disease are needed. Diet is a known modifiable factor in the development of obesity. However, diet only partially explains disease risk. Changes in microbial energy harvesting by the microbiota plays a role in obesity, and the composition of these energy harvesting populations may be controlled by taste receptors. This review explores T2Rs as a potential link between obesity and the human GI microbiome.