Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice

Palma, Giada De; Lynch, Michael D. J.; Lü, Jun; Dang, Vi; Deng, Yikang; Jury, Jennifer; Umeh, Genevieve; Miranda, Pedro Morell; Pastor, Marc Pigrau; Sidani, Sacha; Sánchez, María Inés Pinto; Philip, Vivek; McLean, Peter G.; Hagelsieb, Moreno-Gabriel; Surette, Michael G.; Bergonzelli, Gabriela; Verdú, Elena F.; Britz‐McKibbin, Philip; Neufeld, Josh D.; Collins, Stephen M.; Berčík, Přemysl

doi:10.1126/scitranslmed.aaf6397

Cited by 400 publications

(316 citation statements)

References 98 publications

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“…However, there is concern that more than desired microbes are being transmitted during FMT and that donors need to be carefully screened [125,126]. In one study, germ-free mice receiving fecal microbiota samples from patients with IBS-D exhibited increased GI transit, activation of innate immunity, and altered intestinal barrier function after 3 weeks compared with mice receiving fecal microbiota from healthy individuals [127]. Anxiety-like behavior was evident in mice receiving FMT from patients with IBS-D with anxiety, but not in mice receiving FMT from patients with IBS-D without anxiety or from healthy individuals.…”

Section: Fecal Microbiota Transplantationmentioning

confidence: 99%

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

Harris

Baffy

2017

Postgraduate Medicine

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Irritable bowel syndrome (IBS), which is characterized by recurrent abdominal pain and disordered bowel habits, is one of the most common functional bowel disorders. IBS is a substantial burden on both patient health-related quality of life and healthcare costs. Several pathophysiologic mechanisms have been postulated for the occurrence of IBS, including altered gastrointestinal motility, visceral hypersensitivity, changes in gut permeability, immune activation, gut-brain dysregulation, central nervous system dysfunction, and changes in the gut microbiota. Of note, both qualitative and quantitative differences have been observed in the gut microbiota of a population with IBS versus a healthy population. Because of the substantial interest in the gut microbiota and its role as a therapeutic target in IBS, this article provides an overview of specific interventions with the potential to modulate the gut microbiota in IBS, including elimination diets, prebiotics, probiotics, synbiotics, and nonsystemic antibiotics. Although probiotics and synbiotics are generally well tolerated, differences in the composition and concentration of different bacterial species and inclusion or exclusion of prebiotic components varies widely across studies and has prevented strong recommendations on their use in IBS. For nonsystemic antibiotics, rifaximin is indicated in the United States for the treatment of IBS with diarrhea in adults and has been shown to be efficacious and well tolerated in well-designed clinical trials. Overall, more consistent evidence is needed regarding the efficacy and safety of elimination diets, prebiotics, probiotics, and synbiotics for the treatment of patients with IBS. Furthermore, additional well-designed studies are needed that examine alterations in the gut microbiota that occur with these interventions and their potential associations with clinical symptoms of IBS. ARTICLE HISTORY

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Section: Fecal Microbiota Transplantationmentioning

confidence: 99%

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

Harris

Baffy

2017

Postgraduate Medicine

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“…In a recent study, germ-free mice were colonized by fecal microbiota from 8 patients with diarrhea-predominant irritable bowel syndrome (IBS) and 5 healthy controls. 13 Fecal microbiota analysis of mice showed that it resembled the microbiota of the donor. Authors found that mice receiving microbiota from patients with IBS were more anxious (demonstrated by latency to step-down from the table and time spent in the light box) than those receiving microbiota from healthy subjects; 13 Intestinal transit, paracellular gut permeability, and the molecular markers of gut inflammation were also greater among the former group of mice.…”

mentioning

confidence: 99%

“…13 Fecal microbiota analysis of mice showed that it resembled the microbiota of the donor. Authors found that mice receiving microbiota from patients with IBS were more anxious (demonstrated by latency to step-down from the table and time spent in the light box) than those receiving microbiota from healthy subjects; 13 Intestinal transit, paracellular gut permeability, and the molecular markers of gut inflammation were also greater among the former group of mice. 13 Though the above-mentioned mechanistic studies are important in a scientific perspective, clinicians and patients are interested in knowing whether therapeutic interventions targeting the gut microbiota would have any clinically meaningful alteration in brain functions that may benefit the patients.…”

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confidence: 99%

Gut Microbiota-Brain Axis Modulation by a Healthier Microbiological Microenvironment : Facts and Fictions

Ghoshal

2018

J Neurogastroenterol Motil

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Functions of every organ and system of the body need to be perfectly regulated for the maintenance of the milieu interior; this is performed by a wireless (endocrine) system and a wired (nervous) system in the body. Interestingly, the communication between the brain and the gut is bi-directional; though, the brain controls the gut to a large extent, the gut also influences the brain functions. In recent years, it has been realized that the gut microbiota, which is the largest organ of the human body, influences the brain functions. 1,2 However, this is not entirely a new concept. As early as pre-2nd century CE, in the Charaka Samhita, an Indian book on medicine, it was mentioned that the human being is a microcosmic replica of the universe, 3 and the 3 humors (Vayu or gas, Pitta or bile, and Kapha or mucus) are responsible for most ailments. 4 It is interesting to know how the gastrointestinal tract in general and its microbiota, in particular, is being unraveled by the scientists in recent times.Gut microbial modulation of the brain function is best demonstrated by the well-known effects of gut-microbiota directed antibiotic treatment in patients with hepatic encephalopathy. Moreover, in recent times, several animal and human experiments also demonstrated the role of gut microbiota in influencing brain function. In a study by De Palma et al, 5 germ-free mice were shown to have dysregulated hypothalamic pituitary stress response, altered brainderived neurotrophic factors (BDNF) in the hippocampus, altered neurotransmission, altered tryptophan availability and metabolism, and reduced anxiety. In another experimental study, antibiotic treatment of BALB/c mice resulted in increase in Firmicutes phylum dominated by Lactobacillus, sulfate-reducing bacterial species, and decrease in g-Proteobacteria and Bacteroidetes, which was associated with increase in hippocampal BDNF and autonomic-independent anxiolytic behavior. 6 How does gut microbiota alter brain function? In a study on wild mice separated from their mothers, which is well known to induce anxiety, it was found to be associated with altered gut-microbial colonization, long-lasting hyperactivity of the hypothalamic pituitary-axis, visceral hypersensitivity, altered cholinergic activity in the gut, and increased intestinal permeability. -522-249-4406, Fax: +91-522-2668017, E-mail: udayghoshal@gmail.com Article: Bifidobacterium longum and Lactobacillus helveticus synergistically suppress stress-related visceral hypersensitivity through hypothalamic-pituitary-adrenal axis modulation Ait-Belgnaoui A, Payard I, Rolland C, et al

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“…A recent study by De Palma (1) has shown that fecal material from humans with irritable bowel syndrome (IBS) with diarrhea (IBS-D) invoked physical changes in the intestinal environment and in behavior. This is an interesting outcome, given the questions that have been raised about the relevance of certain models' in light of the differences between the rodent gut physiology, the microbiome and the human condition (2,3).…”

mentioning

confidence: 99%

Transfer of altered behaviour and irritable bowel syndrome with diarrhea (IBS-D) through fecal microbiota transplant in mouse model indicates need for stricter donor screening criteria

Craven¹,

Silverman²,

Burton³

2017

Ann. Transl. Med.

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Experimental studies performing fecal microbiota transplants (FMTs) from human to animals and between animals is providing enlightening information with regards to phenotypical characteristics that can potentially be influenced by the microbiome. A recent study by De Palma (1) has shown that fecal material from humans with irritable bowel syndrome (IBS) with diarrhea (IBS-D) invoked physical changes in the intestinal environment and in behavior. This is an interesting outcome, given the questions that have been raised about the relevance of certain models' in light of the differences between the rodent gut physiology, the microbiome and the human condition (2,3).IBS is characterized by discomfort of the abdomen associated with altered bowel functions, where structural and biochemical abnormalities are absent (4). IBS is prevalent in 11.2% of the global population with more women being affected than men (5). Patients with IBS have significantly higher rates of anxiety and depression than healthy people (6) and they have been shown to have a reduced quality of life (7). IBS can be broken down further into different subtypes including: IBS-D (the focus in this De Palma study), constipation-predominant IBS (IBS-C), mixed-IBS (IBS-M) and unsubtyped IBS (IBS-U).Since IBS is a condition of the gastrointestinal tract, it has been postulated that the disease is caused by alterations in the composition of the gut microbiome. Multiple studies have been conducted trying to determine if patients with IBS have a microbiota that differs from people without the disease. The most conserved finding has been a decrease in diversity of the gut microbiota (8-12). Attempts to identify specific differences in the relative abundances of the gut microbiota of IBS patients have found various results for each study. There is also the possibility that changes in the gut microbiota in IBS patients may be a result of the syndrome, rather than a cause of it, as a variety of other factors may predispose someone to develop IBS, such as genetics, food sensitivities, and food poisoning. Due to the evidence that the microbiota plays a role in the development of IBS, De Palma et al. hypothesized that germ-free mice given a FMT from an IBS-D patient would have altered behaviour, gastrointestinal transit, gut barrier function, and immune activation.In the De Palma study, stool was collected from five healthy controls (HCs) (two men and three women, mean age: 42 years) and eight IBS-D patients (three men and five women, mean age: 40 years). Patients with IBS were diagnosed using the Rome-III criteria and Bristol stool form scale (≥6), with more than three bowel movements per day and symptoms for at least 2 years. Of the IBS-D patients, four were characterized as having anxiety by the Hospital Anxiety and Depression Scale (HADS) (HADS score,(11)(12)(13)(14) and four IBS-D patients did not have anxiety (HADS

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Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice

Cited by 400 publications

References 98 publications

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

Gut Microbiota-Brain Axis Modulation by a Healthier Microbiological Microenvironment : Facts and Fictions

Transfer of altered behaviour and irritable bowel syndrome with diarrhea (IBS-D) through fecal microbiota transplant in mouse model indicates need for stricter donor screening criteria

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