Background and aimsMicrobiota 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.MethodsWe profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103).ResultsSeveral 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.ConclusionThe 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.

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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.The acidic pH in the stomach lumen impedes bacterial growth 1 . However, it is now known that the human stomach is not sterile but is rather colonized by diverse microbiota 2 . High-throughput sequencing of gastric biopsy samples suggests that the human stomach may harbor 128 phyla, although mainly dominated by five phyla, namely, Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes and Fusobacteria 2-5 . Among these, several species of Helicobacter are known to be natural inhabitants of the human stomach. Helicobacter pylori (H. pylori), a Gram-negative bacterium and frequent isolate of stomach specimens, with reported links to the causation of chronic/atrophic gastritis, duodenal ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma 2,6,7 , has coevolved with its human host.While H. pylori has been incriminated in disease, an aspect that has only been recently investigated is the role of the stomach microbiome in the causation of these diseases, especially adenocarcinoma. Studies focusing on the microbial composition of the stomach in healthy individuals 4,[8][9][10] have indicated the presence of genera like Streptococcus, Prevotella, Veillonella, Fusobacterium, Haemophilus and Clostridium. H. pylori is known to utilize specific molecular mechanisms to modulate host immune response and create a local micro-environment that aids its colonization 5,11 . The influence of Helicobacter abundance on the populations of other genera and vice versa, and any interactions between them in the causation ...

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.

Irritable Bowel Syndrome (IBS), the most common gastrointestinal disorder, is diagnosed solely on symptoms. Potentially diagnostic alterations in the bacterial component of the gut microbiome (the bacteriome) are associated with IBS, but despite the known role of the virome (particularly bacteriophages), in shaping the gut bacteriome, few studies have investigated the virome in IBS. We performed metagenomic sequencing of fecal Virus-Like Particles (VLPs) from 55 patients with IBS and 51 control individuals. We detected significantly lower alpha diversity of viral clusters comprising both known and novel viruses (viral ‘dark matter’) in IBS and a significant difference in beta diversity compared to controls, but not between IBS symptom subtypes. The three most abundant bacteriophage clusters belonged to the Siphoviridae, Myoviridae , and Podoviridae families (Order Caudovirales ). A core virome (defined as a cluster present in at least 50% of samples) of 5 and 12 viral clusters was identified in IBS and control subjects, respectively. We also identified a subset of viral clusters that showed differential abundance between IBS and controls. The virome did not co-vary significantly with the bacteriome, with IBS clinical subtype, or with Bile Acid Malabsorption status. However, differences in the virome could be related back to the bacteriome as analysis of CRISPR spacers indicated that the virome alterations were at least partially related to the alterations in the bacteriome. We found no evidence for a shift from lytic to lysogenic replication of core viral clusters, a phenomenon reported for the gut virome of patients with Inflammatory Bowel Disease. Collectively, our data show alterations in the virome of patients with IBS, regardless of clinical subtype, which may facilitate development of new microbiome-based therapeutics.

Alterations of the gut microbiota have been reported in various gastrointestinal disorders, but knowledge of the mycobiome is limited. We investigated the gut mycobiome of 80 patients with Irritable Bowel Syndrome (IBS) in comparison with 64 control subjects. The fungal-specific internal transcribed spacer 1 (ITS-1) amplicon was sequenced, and mycobiome zero-radius operational taxonomic units (zOTUs) were defined representing known and unknown species and strains. The fungal community was sparse and individual-specific in all (both IBS and control) subjects. Although beta-diversity differed significantly between IBS and controls, no difference was found among clinical subtypes of IBS or in comparison with the mycobiome of subjects with bile acid malabsorption (BAM), a condition which may overlap with IBS with diarrhoea. The mycobiome alterations co-varied significantly with the bacteriome and metabolome but were not linked with dietary habits. As a putative biomarker of IBS, the predictive power of the fecal mycobiome in machine learning models was significantly better than random but insufficient for clinical diagnosis. The mycobiome presents limited therapeutic and diagnostic potential for IBS, despite co-variation with bacterial components which do offer such potential.

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