Bacteria that colonize the mammalian intestine collectively possess a far larger repertoire of degradative enzymes and metabolic capabilities than their hosts. Microbial fermentation of complex non...

https://www.tandfonline.com/doi/pdf/10.4161/gmic.19897

Microbial degradation of complex carbohydrates in the gut

It is increasingly perceived that gut host–microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID) The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS Investigators are also starting to measure host–microbial interactions in IBS The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system While we await important insights in this field, the microbiota is already a therapeutic target Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions The authors also provide clinical guidance on modulation of gut microbiota in IBS

https://gut.bmj.com/content/gutjnl/62/1/159.full.pdf

Intestinal microbiota in functional bowel disorders: a Rome foundation report

A compendium of all the volatile organic compounds (VOCs) emanating from the human body (the volatolome) is for the first time reported. 1840 VOCs have been assigned from breath (872), saliva (359), blood (154), milk (256), skin secretions (532) urine (279), and faeces (381) in apparently healthy individuals. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been grouped into tables according to their chemical class or functionality to permit easy comparison. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces. Careful use of the database is needed. The numbers may not be a true reflection of the actual VOCs present from each bodily excretion. The lack of a compound could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from blood compared to a large number on VOCs in breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. collecting excretions on glass beads and then heating to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors' intention that this database will not only be a useful database of VOCs listed in the literature, but will stimulate further study of VOCs from healthy individuals. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.

https://iopscience.iop.org/article/10.1088/1752-7155/8/1/014001/pdf

A review of the volatiles from the healthy human body

Objective The assessment of potentially confounding factors affecting colon microbiota composition is essential to the identification of robust microbiome based disease markers. Here, we investigate the link between gut microbiota variation and stool consistency using Bristol Stool Scale classification, which reflects faecal water content and activity, and is considered a proxy for intestinal colon transit time. Design Through 16S rDNA Illumina profiling of faecal samples of 53 healthy women, we evaluated associations between microbiome richness, Bacteroidetes:Firmicutes ratio, enterotypes, and genus abundance with self-reported, Bristol Stool Scale-based stool consistency. Each sample’s microbiota growth potential was calculated to test whether transit time acts as a selective force on gut bacterial growth rates. Results Stool consistency strongly correlates with all known major microbiome markers. It is negatively correlated with species richness, positively associated to the Bacteroidetes:Firmicutes ratio, and linked to Akkermansia and Methanobrevibacter abundance. Enterotypes are distinctly distributed over the BSS-scores. Based on the correlations between microbiota growth potential and stool consistency scores within both enterotypes, we hypothesise that accelerated transit contributes to colon ecosystem differentiation. While shorter transit times can be linked to increased abundance of fast growing species in Ruminococcaceae- Bacteroides samples, hinting to a washout avoidance strategy of faster replication, this trend is absent in Prevotella -enterotyped individuals. Within this enterotype adherence to host tissue therefore appears to be a more likely bacterial strategy to cope with washout. Conclusions The strength of the associations between stool consistency and species richness, enterotypes and community composition emphasises the crucial importance of stool consistency assessment in gut metagenome-wide association studies.

https://gut.bmj.com/content/gutjnl/65/1/57.full.pdf

Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates

Background

Postoperative ileus has traditionally been accepted as a normal response to tissue injury. No data support any beneficial effect of ileus and indeed it may contribute to delayed recovery and prolonged hospital stay. Efforts should, therefore, be made to reduce such ileus.



Methods

Material was identified from a Medline search of the literature, previous review articles and references cited in original papers. This paper updates knowledge on the pathophysiology and treatment of postoperative ileus.



Results and conclusion

Pathogenesis mainly involves inhibitory neural reflexes and inflammatory mediators released from the site of injury. The most effective method of reducing ileus is thoracic epidural blockade with local anaesthetic. Opioid-sparing analgesic techniques and non-steroidal anti-inflammatory agents also reduce ileus, as does laparoscopic surgery. Of the prokinetic agents only cisapride is proven beneficial; the effect of early enteral feeding remains unclear. However, postoperative ileus may be greatly reduced when all of the above are combined in a multimodal rehabilitation strategy. © 2000 British Journal of Surgery Society Ltd

Postoperative ileus: a preventable event

The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air (P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/- 301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.

https://www.physiology.org/doi/pdf/10.1152/ajpgi.00574.2004

Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity

Evidence points to a significant overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). In this study, we evaluate this overlap by conducting a systematic review of the literature. Six electronic databases from 1966 through January 2005 were screened by multiple search terms to identify all epidmiological evidence linking IBS and GERD. In addition, AGA meeting abstracts for 2003 and 2004 were also screened. All studies were validated by the authors and data extracted according to predefined criteria. As a separate search strategy, studies evaluating the prevalence of IBS and GERD in the general population were sought. These articles were obtained to compare the prevalence of IBS and GERD in the community to the degree of overlap. The search identified 997 original titles with 15 publications that fulfilled our eligibility criteria. Among the 15 studies, 7 determined the GERD maximum mean prevalence in patients already diagnosed with IBS to be 39.3% and the weighted mean 30.3%. The other 7 studies examined the prevalence of IBS in patients already diagnosed with GERD. The maximum mean prevalence of IBS in subjects with known GERD was 48.8% and the weighted mean 60.5%. Based on the prevalence of IBS (12.1%) and GERD (19.4%) in the community, the rate of IBS in the non-GERD community was calculated to be only 5.1%. There is a strong overlap between GERD and IBS that exceeds the individual presence of each condition. In the absence of GERD, IBS is relatively uncommon.

Studying the overlap between IBS and GERD: a systematic review of the literature.

OBJECTIVE To compare colonic microbial composition in systemic sclerosis (SSc) patients and healthy controls and to determine whether certain microbial genera are associated with gastrointestinal (GI) tract symptoms in patients with SSc. METHODS Healthy controls were age- and sex-matched (1:1) with adult SSc patients. Cecum and sigmoid mucosal lavage samples were obtained during colonoscopy. The microbiota in these samples were determined by Illumina HiSeq 2000 16S sequencing, and operational taxonomic units were selected. Linear discriminant analysis effect size was used to identify the genera that showed differential expression in SSc patients versus controls. Differential expression analysis for sequence count data was used to identify specific genera associated with GI tract symptoms. RESULTS Among 17 patients with SSc (88% female; median age 52.1 years), the mean ± SD total GI Tract 2.0 score was 0.7 ± 0.6. Principal coordinate analysis illustrated significant differences in microbial communities in the cecum and sigmoid regions in SSc patients versus healthy controls (both P = 0.001). Similar to the findings in inflammatory disease states, SSc patients had decreased levels of commensal bacteria, such as Faecalibacterium and Clostridium, and increased levels of pathobiont bacteria, such as Fusobacterium and γ-Proteobacteria, compared with healthy controls. Bifidobacterium and Lactobacillus, which are typically reduced under conditions of inflammation, were also increased in abundance in patients with SSc. In SSc patients with moderate/severe GI tract symptoms, the abundance of Bacteroides fragilis was decreased, and that of Fusobacterium was increased, compared with patients who had no or mild symptoms. CONCLUSION This study demonstrates a distinct colonic microbial signature in SSc patients compared with healthy controls. This unique ecologic change may perpetuate immunologic aberrations and contribute to clinical manifestations of SSc.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.39572

Association of Systemic Sclerosis With a Unique Colonic Microbial Consortium

Ischemia-reperfusion injury leads to profound functional and structural alterations of the gastrointestinal tract. We developed an in vitro model of reperfusion injury to study the changes in intestinal motility during hypoxia followed by reoxygenation. We recorded the spontaneous motor activity of intestinal rings from the proximal mouse jejunum, using force displacement transducers. In addition to the rhythmic contractions, we studied the contractile response to transmural stimulation of intrinsic nerves. During hypoxia, the frequency of the spontaneous contractions and the resting tension decreased. While 29% of the tissues still responded to neural stimulation after 15 min of hypoxia, electrical field stimulation did not evoke any response after 60 min of hypoxia. Reoxygenation resulted in a transient increase in the baseline tension and an initial normalization of the spontaneous rhythmic contractions, which subsequently became irregular. The percentage of tissues that recovered their ability to respond to electrical field stimulation 10 min after reoxygenation decreased from 100% after 15 min of hypoxia to 47% after 60 min of hypoxia. The administration of the antioxidant glutathione prevented the functional abnormalities seen 10 min after reoxygenation. The pharmacological inhibition of Cu,Zn superoxide dismutase exacerbated the functional reoxygenation damage. Conversely, the overexpression of this radical-scavenging enzyme in transgenic mice increased the likelihood of functional recovery. Reoxygenation in a calcium-free solution also prevented prolonged functional damage of the muscle rings. We conclude that hypoxia-reoxygenation significantly alters intestinal motility. The generation of reactive oxygen species and disruptions in the calcium homeostasis play an important role in the pathogenesis of reoxygenation damage. Interventions that alter the intracellular redox state or affect the secondary changes in the intracellular calcium concentration can prevent or blunt the effects of reoxygenation injury on intestinal motility.

Jeffrey L. Conklin

Papers

Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity

Studying the overlap between IBS and GERD: a systematic review of the literature.

Association of Systemic Sclerosis With a Unique Colonic Microbial Consortium

Intestinal Motility During Hypoxia and Reoxygenation in Vitro

Lactose intolerance and the role of the lactose breath test.