Farncombe Family Digestive Health Research Institute

Ontario, Canada

Farncombe Family Digestive Health Research Institute

Ontario, Canada

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The bacteria in our gut have become very popular lately. Whether we are debunking probiotics, understanding antibiotics, deciding on our diet or trying to feel happier, the influence of these microbes seems to be everywhere in our daily lives. A growing body of research justifies that attention. Recent studies have revealed not only the diversity of species living in our inner bacterial gardens but also the significant role they play in our physical and mental health. One recent study discerning the importance of the gut microbiome-brain axis—the scientific terminology for the connection between our bellies and brains—confirms the strong link between the two. Researchers from the University of California, Los Angeles’s David Geffen School of Medicine found an association between these microbes and sensory areas of the brain in people with irritable bowel syndrome (IBS), an intestinal disorder. And it’s the first study to find this link in humans. Trending: Turkey Warns U.S. of Blowback From Decision to Arm Kurds in Syria Related: White House goes with its gut, launching microbiome initiative Emeran Mayer and his colleagues collected behavioral information, stool samples and brain images from 29 adults with IBS and 23 healthy people. They used gene sequencing to identify the microbes present in the collection of stool samples and also determined the abundance and diversity of bacteria in each participant’s fecal matter. The IBS patients fell into two groups, distinguished by their microbiomes. In one group, the collection of bacterial species was similar to that of the healthy patients. In the other group, the collection was more distinct. Now for the behavior. The researchers wanted to know if the microbiomes of the IBS patients showed any association with psychological or emotional distress of any kind. They used an anxiety and depression scale and a health questionnaire to gather information, and they also asked patients about childhood trauma and other adversities they’d experienced before age 18. They gauged how stressed-out the patients were and checked what medications they’d been taking. It turned out that the two IBS groups did not vary all that much in their behavior. IBS patients whose microbiomes were more distinct from healthy participants reported more emotional issues. But this IBS microbial community was not associated with heightened depression, stress or medication use. However, there were surprising differences between the groups. Instead of manifesting in their emotions and mental health, these variations showed up in their brains. The images of certain sensory regions of the brain—the thalamus, the basal ganglia and the sensory motor cortex—showed differences for the IBS patients with the distinct microbiome, compared with the healthy subjects. Mayer explains that the sensory differences seen among the bacterially distinct IBS patients could be connected to the food sensitivities that IBS patients often have. Individuals may complain of abdominal pain after eating or taking certain medications, for example. “I think all this is related to a fundamental change in the way that the brain processes any sensory [disturbance],” says Mayer. The findings are the first to show an association between the gut microbiome of IBS patients and structural alterations in the brain. However, Mayer emphasizes that the association does not explain the cause. “The study is exploratory,” says Elyanne Ratcliffe, a pediatrician at the Farncombe Family Digestive Health Research Institute at Canada’s McMaster University. “There are some plausible pathways, but it has to be worked out more rigorously.” Ratcliffe also cautions against zeroing in on any particular brain image connection. “If you look at tons of stuff, you’re bound to find something,” she says. Most popular: Why Is China’s Xi Cracking Down on Free Speech? The direction of that pathway is also in question. If the brain and gut microbiome are connected, which determines which? Does the brain influence gut development, or does the gut influence brain development? Mayer believes it’s a two-way street. “Signals from the gut microbes shape the way the sensory system develops,” he says. His theory, which he describes at length in his book, The Mind-Gut Connection, is that our microbial communities assemble early in life, when the brain is still very flexible. The microbiome of an infant’s gut is created through the nutrition he or she receives from the mother, how that nutrition is delivered and other factors. It is possible, though not yet proved, that if the mother experienced stress during pregnancy, that might also influence the developing infant’s microbial community. Early-life trauma has also been found to shape the gut microbiome. “A lot of influences start during pregnancy and go on for the first three years of life,” says Mayer. “That’s the programming of the gut microbiome-brain axis.” The established microbiome then influences the brain, and then the brain continues to influence the microbiome, in a lifelong loop. Related: Antibodies in breast milk prime the baby’s gut to handle Mom’s invading microbes The UCLA researchers, along with a host of other scientists worldwide, are continuing to study the link between the gut microbiome and brain development. Whether a problematic microbiome can be altered is another matter altogether. But, says Mayer, a diet that includes a diversity of microbes—namely, one consisting mainly of plants—is probably the best approach in the absence of further evidence. Scientists do not yet understand the implications of the gut microbiome, and any interpretations of the ongoing research are still controversial and iffy. Studies continue to probe the influence of our inner flora on IBS, autism spectrum disorders and our general health (several were just presented at Digestive Disease Week). But none so far have offered concrete proof of these links. In addition, scientists are still trying to parse which bacterial species make for the ideal gut garden. Related: A large microbiome study says wine and coffee help keep your gut bacteria diverse and healthy The 'Second Brain' in Our Bellies and How it Controls Digestion


News Article | May 23, 2017
Site: www.eurekalert.org

Hamilton, ON (May 23, 2017) - Probiotics may relieve symptoms of depression, as well as help gastrointestinal upset, research from McMaster University has found. In a study published in the medical journal Gastroenterology (May 2), researchers of the Farncombe Family Digestive Health Research Institute found that twice as many adults with irritable bowel syndrome (IBS) reported improvements from co-existing depression when they took a specific probiotic than adults with IBS who took a placebo. The study provides further evidence of the microbiota environment in the intestines being in direct communication with the brain said senior author Dr. Premysl Bercik, an associate professor of medicine at McMaster and a gastroenterologist for Hamilton Health Sciences. "This study shows that consumption of a specific probiotic can improve both gut symptoms and psychological issues in IBS. This opens new avenues not only for the treatment of patients with functional bowel disorders but also for patients with primary psychiatric diseases," he said. IBS is the most common gastrointestinal disorder in the world, and is highly prevalent in Canada. It affects the large intestine and patients suffer from abdominal pain and altered bowel habits like diarrhea and constipation. They are also frequently affected by chronic anxiety or depression. The pilot study involved 44 adults with IBS and mild to moderate anxiety or depression. They were followed for 10 weeks, as half took a daily dose of the probiotic Bifidobacterium longum NCC3001, while the others had a placebo. At six weeks, 14 of 22, or 64%, of the patients taking the probiotic had decreased depression scores, compared to seven of 22 (or 32%) of patients given placebo. Functional Magnetic Resonance Imaging (fMRI) showed that the improvement in depression scores was associated with changes in multiple brain areas involved in mood control. "This is the result of a decade long journey - from identifying the probiotic, testing it in preclinical models and investigating the pathways through which the signals from the gut reach the brain," said Bercik. "The results of this pilot study are very promising but they have to be confirmed in a future, larger scale trial," said Dr. Maria Pinto Sanchez, the first author and a McMaster clinical research fellow. The study was performed in collaboration with scientists from Nestlé. For more information: Veronica McGuire Media Relations Faculty of Health Sciences McMaster University vmcguir@mcmaster.ca 905-525-9140, ext. 22169


News Article | May 25, 2017
Site: www.sciencedaily.com

Probiotics may relieve symptoms of depression, as well as help gastrointestinal upset, research from McMaster University has found. In a study published in the medical journal Gastroenterology, researchers of the Farncombe Family Digestive Health Research Institute found that twice as many adults with irritable bowel syndrome (IBS) reported improvements from co-existing depression when they took a specific probiotic than adults with IBS who took a placebo. The study provides further evidence of the microbiota environment in the intestines being in direct communication with the brain said senior author Dr. Premysl Bercik, an associate professor of medicine at McMaster and a gastroenterologist for Hamilton Health Sciences. "This study shows that consumption of a specific probiotic can improve both gut symptoms and psychological issues in IBS. This opens new avenues not only for the treatment of patients with functional bowel disorders but also for patients with primary psychiatric diseases," he said. IBS is the most common gastrointestinal disorder in the world, and is highly prevalent in Canada. It affects the large intestine and patients suffer from abdominal pain and altered bowel habits like diarrhea and constipation. They are also frequently affected by chronic anxiety or depression. The pilot study involved 44 adults with IBS and mild to moderate anxiety or depression. They were followed for 10 weeks, as half took a daily dose of the probiotic Bifidobacterium longum NCC3001, while the others had a placebo. At six weeks, 14 of 22, or 64%, of the patients taking the probiotic had decreased depression scores, compared to seven of 22 (or 32%) of patients given placebo. Functional Magnetic Resonance Imaging (fMRI) showed that the improvement in depression scores was associated with changes in multiple brain areas involved in mood control. "This is the result of a decade long journey -- from identifying the probiotic, testing it in preclinical models and investigating the pathways through which the signals from the gut reach the brain," said Bercik. "The results of this pilot study are very promising but they have to be confirmed in a future, larger scale trial," said Dr. Maria Pinto Sanchez, the first author and a McMaster clinical research fellow.


Kassam Z.,McMaster University | Lee C.H.,McMaster University | Lee C.H.,Hamilton Regional Laboratory Medicine Program | Yuan Y.,McMaster University | And 3 more authors.
American Journal of Gastroenterology | Year: 2013

OBJECTIVES: The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.METHODS: An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.RESULTS: Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I 2 =33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI-0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.CONCLUSIONS: FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated. © 2013 by the American College of Gastroenterology.


News Article | March 2, 2017
Site: www.biosciencetechnology.com

Research from McMaster University has found that bacteria in the gut impacts both intestinal and behavioral symptoms in patients suffering from irritable bowel syndrome (IBS), a finding which could lead to new microbiota-directed treatments. The new study, published today in Science Translational Medicine, was led by researchers from the Farncombe Family Digestive Health Research Institute at McMaster, Drs. Premysl Bercik and Stephen Collins, in collaboration with researchers from the University of Waterloo. IBS is the most common gastrointestinal disorder in the world. It affects the large intestine and patients suffer from abdominal pain and altered bowel habits like diarrhea and constipation, which are often accompanied by chronic anxiety or depression. Current treatments aimed at improving symptoms have limited efficacy because the underlying causes are unknown. The goal of the study was to explore whether fecal microbiota from human IBS patients with diarrhea has the ability to influence gut and brain function in recipient mice. Using fecal transplants, researchers transferred microbiota from IBS patients with or without anxiety into germ-free mice. The mice went on to develop changes both in intestinal function and behavior reminiscent of the donor IBS patients, compared to mice that were transplanted with microbiota from healthy individuals. The researchers found that aspects of the illness that were impacted through fecal transplants included gastrointestinal transit (the time it takes for food to leave the stomach and travel through the intestine); intestinal barrier dysfunction; low grade inflammation; and anxiety-like behavior. "This is a landmark study because it moves the field beyond a simple association, and towards evidence that changes in the microbiota impact both intestinal and behavioral responses in IBS," said Giada De Palma, the study's first author and research associate with the Farncombe Family Digestive Health Research Institute. "Our findings provide the basis for developing therapies aimed at the intestinal microbiota, and for finding biomarkers for the diagnosis of IBS," said Premysl Bercik, the study's lead author and Associate Professor of Medicine at McMaster University. The authors conclude that their findings raise the possibility that "microbiota-directed therapies, including pre- or probiotic treatment, may be beneficial in treating not only intestinal symptoms but also components of the behavioral manifestations of IBS." Interestingly, the authors noted that since the study showed that microbiota in the gut can influence the brain, it "adds to evidence suggesting that the intestinal microbiota may play some role in the spectrum of brain disorders ranging from mood or anxiety to other problems that may include autism, Parkinson's disease and multiple sclerosis." However, they added that further work is required to better define the relationship in these conditions.


News Article | March 1, 2017
Site: www.eurekalert.org

Hamilton, ON (March 1, 2017) - Research from McMaster University has found that bacteria in the gut impacts both intestinal and behavioural symptoms in patients suffering from irritable bowel syndrome (IBS), a finding which could lead to new microbiota-directed treatments. The new study, published today in Science Translational Medicine, was led by researchers from the Farncombe Family Digestive Health Research Institute at McMaster, Drs. Premysl Bercik and Stephen Collins, in collaboration with researchers from the University of Waterloo. IBS is the most common gastrointestinal disorder in the world. It affects the large intestine and patients suffer from abdominal pain and altered bowel habits like diarrhea and constipation, which are often accompanied by chronic anxiety or depression. Current treatments aimed at improving symptoms have limited efficacy because the underlying causes are unknown. The goal of the study was to explore whether fecal microbiota from human IBS patients with diarrhea has the ability to influence gut and brain function in recipient mice. Using fecal transplants, researchers transferred microbiota from IBS patients with or without anxiety into germ-free mice. The mice went on to develop changes both in intestinal function and behavior reminiscent of the donor IBS patients, compared to mice that were transplanted with microbiota from healthy individuals. The researchers found that aspects of the illness that were impacted through fecal transplants included gastrointestinal transit (the time it takes for food to leave the stomach and travel through the intestine); intestinal barrier dysfunction; low grade inflammation; and anxiety-like behaviour. "This is a landmark study because it moves the field beyond a simple association, and towards evidence that changes in the microbiota impact both intestinal and behavioral responses in IBS," said Giada De Palma, the study's first author and research associate with the Farncombe Family Digestive Health Research Institute. "Our findings provide the basis for developing therapies aimed at the intestinal microbiota, and for finding biomarkers for the diagnosis of IBS," said Premysl Bercik, the study's lead author and Associate Professor of Medicine at McMaster University. The authors conclude that their findings raise the possibility that "microbiota-directed therapies, including pre- or probiotic treatment, may be beneficial in treating not only intestinal symptoms but also components of the behavioural manifestations of IBS." Interestingly, the authors noted that since the study showed that microbiota in the gut can influence the brain, it "adds to evidence suggesting that the intestinal microbiota may play some role in the spectrum of brain disorders ranging from mood or anxiety to other problems that may include autism, Parkinson's disease and multiple sclerosis." However, they added that further work is required to better define the relationship in these conditions. This study was supported by grants from CIHR and Nestle Switzerland.


Ford A.C.,Farncombe Family Digestive Health Research Institute | Thabane M.,Farncombe Family Digestive Health Research Institute | Collins S.M.,Farncombe Family Digestive Health Research Institute | Moayyedi P.,Farncombe Family Digestive Health Research Institute | And 3 more authors.
Gastroenterology | Year: 2010

Background & Aims: Symptoms of dyspepsia may occur following an episode of acute gastroenteritis, but data are conflicting. We assessed prevalence of uninvestigated dyspepsia in a cohort of individuals, some of whom were exposed to bacterial dysentery in May 2000, as well as risk factors for dyspepsia in exposed individuals. Methods: This was a cohort study conducted in the town of Walkerton, Ontario, Canada. Involved individuals were recruited into the Walkerton Health Study between 2002 and 2003 and were attending for annual assessment in 2008. Exposed individuals were subdivided into those with self-reported gastroenteritis, with acute illness unconfirmed by health records, and those with clinically confirmed gastroenteritis, with substantiation of acute illness by health record review. Presence of dyspepsia at 8 years, according to a broad definition (any symptom referable to the upper gastrointestinal tract), and the Rome II criteria, was compared between exposed and nonexposed individuals. Results: Of 2597 subjects eligible, 1088 (41.9%) provided data for analysis, and 706 (64.9%) had reported acute gastroenteritis. Multivariate odd ratios for dyspepsia at 8 years in exposed individuals using a broad definition and the Rome II definition were 2.09 (95% confidence interval: 1.58-2.78) and 2.30 (95% confidence interval: 1.63-3.26), respectively. Prevalence of dyspepsia was higher in females; smokers; those with premorbid irritable bowel syndrome, anxiety, or depression; and those reporting >7 days of diarrhea or abdominal cramps during the acute illness. Conclusions: Symptoms of dyspepsia 8 years after an outbreak of acute gastroenteritis were significantly more prevalent in exposed compared with nonexposed individuals. © 2010 AGA Institute.


Shajib M.S.,Farncombe Family Digestive Health Research Institute | Shajib M.S.,McMaster University | Khan W.I.,Farncombe Family Digestive Health Research Institute | Khan W.I.,McMaster University | Khan W.I.,Hamilton Health Sciences
Acta Physiologica | Year: 2015

Serotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter and hormone that contributes to the regulation of various physiological functions by its actions in the central nervous system (CNS) and in the respective organ systems. Peripheral 5-HT is predominantly produced by enterochromaffin (EC) cells of the gastrointestinal (GI) tract. These gut-resident cells produce much more 5-HT than all neuronal and other sources combined, establishing EC cells as the main source of this biogenic amine in the human body. Peripheral 5-HT is also a potent immune modulator and affects various immune cells through its receptors and via the recently identified process of serotonylation. Alterations in 5-HT signalling have been described in inflammatory conditions of the gut, such as inflammatory bowel disease. The association between 5-HT and inflammation, however, is not limited to the gut, as changes in 5-HT levels have also been reported in patients with allergic airway inflammation and rheumatoid arthritis. Based on searches for terms such as '5-HT', 'EC cell', 'immune cells' and 'inflammation' in pubmed.gov as well as by utilizing pertinent reviews, the current review aims to provide an update on the role of 5-HT in biological functions with a particular focus on immune activation and inflammation. © 2015 Scandinavian Physiological Society.


News Article | August 24, 2016
Site: www.chromatographytechniques.com

About 40 percent of the population have a genetic disposition to celiac disease, but only about one percent develop the autoimmune condition when exposed to gluten, and this could be promoted by the type of bacteria present in the gut. Researchers at McMaster University have found that gluten, a common protein in the Western diet that is not well digested by the gut enzymes, could be metabolized by bacteria. The scientists of the Farncombe Family Digestive Health Research Institute at McMaster University discovered that mice that harbored in their gut the opportunistic bacteria Pseudomonas aeruginosa (Psa) isolated from celiac patients, metabolized gluten differently than mice treated with Lactobacillus, often used as probiotics. More interestingly, when the chemistry of gluten metabolism by Psa and Lactobacillus were analyzed, the researchers found that Psa produced gluten sequences that stimulated inflammation in celiac patients, while Lactobacillus was able to detoxify gluten. The paper, published online in the international medical journal Gastroenterology, was funded by a grant from the Canadian Institutes for Health Research and involved researchers in Canada, Australia and Germany. "So the type of bacteria that we have in our gut contributes to the digestion of gluten, and the way this digestion is performed could increase or decrease the chances of developing celiac disease in a person with genetic risk," said Elena Verdu, senior author of the study and an associate professor of medicine for the Michael G. DeGroote School of Medicine at McMaster. "Celiac disease is caused by gluten in genetically predisposed people, but bacteria in our gut could tip the balance in some people between developing the disease or staying healthy." Celiac disease is the inflammatory reaction triggered by eating gluten, which is a group of proteins found in wheat, rye and barley, and which leads to destruction of the gut lining. The number of people who suffer from celiac disease has been steadily increasing in the past decade, and some researchers feel it may be blamed on environmental factors. "We may be closer to understanding the way gut bacteria and opportunistic pathogens such as Psa could affect celiac disease risk. This will help us develop strategies to prevent these disorders, but more research is needed," said Verdu.


McClemens J.,Farncombe Family Digestive Health Research Institute
Clinical and vaccine immunology : CVI | Year: 2013

Enteric parasite infections around the world are a huge economic burden and decrease the quality of life for many people. The use of beneficial bacteria has attracted attention for their potential therapeutic applications in various diseases. However, the effects of beneficial bacteria in enteric parasitic infections remain largely unexplored. We investigated the effects of ingestion of Lactobacillus rhamnosus (JB-1) in a model of enteric nematode (Trichuris muris) infection. C57BL/6 (resistant to infection), AKR (susceptible to infection), interleukin 10 (IL-10) knockout (KO), and mucin Muc2 KO mice were infected with T. muris and treated orally with probiotic JB-1 or medium. The mice were sacrificed on various days postinfection to examine goblet cells, epithelial cell proliferation, cytokines, and worm burdens. Treatment with JB-1 significantly enhanced worm expulsion in resistant C57BL/6 mice, and this was associated with increases in IL-10 levels, goblet cell numbers, and epithelial cell proliferation. Beneficial effects of JB-1 were absent in IL-10 KO and resistant mice treated with γ-irradiated bacteria. Live JB-1 treatment also expedited worm expulsion in Muc2 KO mice and, more importantly, in AKR mice (susceptible to infection). Injection of IL-10 directly into the colonic tissue of uninfected mice induced goblet cell hyperplasia. These findings demonstrate that JB-1 modulates goblet cell biology and promotes parasite expulsion via an IL-10-mediated pathway and provide novel insights into probiotic effects on innate defense in nematode infection.

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