Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a heterogeneous disorder, but diagnoses and determination of subtypes are made based on symptoms. We profiled the fecal microbiomes of patients with and without IBS to identify biomarkers of this disorder. METHODS: We collected fecal and urine samples from 80 patients with IBS (Rome IV criteria; 16-70 years old) and 65 matched individuals without IBS (control individuals), along with anthropometric, medical, and dietary information. Shotgun and 16S ribosomal RNA amplicon sequencing were performed on feces, whereas urine and fecal metabolites were analyzed by gas chromatography and liquid chromatography-mass spectrometry. Co-occurrence networks were generated based on significant Spearman correlations between data. Bile acid malabsorption (BAM) was identified in patients with diarrhea by retention of radiolabeled selenium-75 homocholic acid taurine. RESULTS: Patients with IBS had significant differences in network connections between diet and fecal microbiomes compared with control individuals; these were accompanied by differences in fecal metabolomes. We did not find significant differences in fecal microbiota composition among patients with different IBS symptom subtypes. Fecal metabolome profiles could discriminate patients with IBS from control individuals. Urine metabolomes also differed significantly between patients with IBS and control individuals, but most discriminatory metabolites were related to diet or medications. Fecal metabolomes, but not microbiomes, could distinguish patients with IBS with vs those without BAM. CONCLUSIONS: Despite the heterogeneity of IBS, patients have significant differences in urine and fecal metabolomes and fecal microbiome vs control individuals, independent of symptom-based subtypes of IBS. Fecal metabolome analysis can be used to distinguish patients with IBS with vs those without BAM. These findings might be used for developing microbe-based treatments for these disorders.

The oral microbiota in colorectal cancer is distinctive and predictive.

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 screening for CRC. METHODS: We profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103). RESULTS: Several oral taxa were differentially abundant in CRC compared with controls, for example, Streptococcus and Prevotellas pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC-associated oral bacteria such as Peptostreptococcus, Parvimonas and Fusobacterium were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet. CONCLUSION: The heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC.

Gastric microbiome of Indian patients with Helicobacter pylori infection, and their interaction networks.

The gastric microbiome is suspected to have a role in the causation of diseases by Helicobacter pylori. Reports on their relative abundance vis-à-vis H. pylori are available from various ethnic and geographic groups, but little is known about their interaction patterns. Endoscopic mucosal biopsy samples from the gastric antrum and corpus of 39 patients with suspected H. pylori infection were collected and microbiomes were analyzed by 16S rDNA profiling. Four groups of samples were identified, which harbored Helicobacter as well as a diverse group of bacteria including Lactobacillus, Halomonas and Prevotella. There was a negative association between the microbiome diversity and Helicobacter abundance. Network analyses showed that Helicobacter had negative interactions with members of the gastric microbiome, while other microbes interacted positively with each other, showing a higher tendency towards intra-cluster co-occurrence/co-operation. Cross-geographic comparisons suggested the presence of region-specific microbial abundance profiles. We report the microbial diversity, abundance variation and interaction patterns of the gastric microbiota of Indian patients with H. pylori infection and present a comparison of the same with the gastric microbial ecology in samples from different geographic regions. Such microbial abundance profiles and microbial interactions can help in understanding the pathophysiology of gastric ailments and can thus help in development of new strategies to curb it.

Xenobiotic Metabolism and Gut Microbiomes.

Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome) in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs) also indicate geographic as well as age specific trends.

Nanoceria based electrochemical sensor for hydrogen peroxide detection.

Oxidative stress is a condition when the concentration of free radicals and reactive molecular species rise above certain level in living systems. This condition not only perturbs the normal physiology of the system but also has been implicated in many diseases in humans and other animals. Hydrogen peroxide (H2O2) is known to be involved in induction of oxidative stress and has also been linked to a variety of ailments such as inflammation, rheumatoid arthritis, diabetes, and cancer in humans. It is one of the more stable reactive molecular species present in living systems. Because of its stability and links with various diseases, sensing the level of H2O2 can be of great help in diagnosing these diseases, thereby easing disease management and amelioration. Nanoceria is a potent candidate in free radical scavenging as well as sensing because of its unique redox properties. These properties have been exploited, in the reported work, to sense and quantify peroxide levels. Nanoceria has been synthesized using different capping agents: Hexamethylene-tetra-amine (HMTA) and fructose. CeO2-HMTA show rhombohedral and cubic 6.4 nm particles whereas CeO2-fructose are found to be spherical with average particle diameter size 5.8 nm. CeO2-HMTA, due to the better exposure of the active (200) and (220) planes relative to (111) plane, exhibits superior electrocatalytic activity toward H2O2 reduction. Amperometric responses were measured by increasing H2O2 concentration. The authors observed a sensitivity of 21.13 and 9.6 µA cm(-2) mM(-1) for CeO2-HMTA and CeO2-fructose, respectively. The response time of 4.8 and 6.5 s was observed for CeO2-HMTA and CeO2-fructose, respectively. The limit of detection is as low as 0.6 and 2.0 µM at S/N ratio 3 for CeO2-HMTA and CeO2-fructose, respectively. Ceria-HMTA was further tested for its antioxidant activity in an animal cell line in vitro and the results confirmed its activity.