Reproducible and opposing gut microbiome signatures distinguish autoimmune diseases and cancers: a systematic review and meta-analysis

Abstract

Background The gut microbiome promotes specific immune responses, and in turn, the immune system has a hand in shaping the microbiome. Cancer and autoimmune diseases are two major disease families that result from the contrasting manifestations of immune dysfunction. We hypothesized that the opposing immunological profiles between cancer and autoimmunity yield analogously inverted gut microbiome signatures. To test this, we conducted a systematic review and meta-analysis on gut microbiome signatures and their directionality in cancers and autoimmune conditions. Methodology We searched PubMed, Web of Science, and Embase to identify relevant articles to be included in this study. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements and PRISMA 2009 checklist. Study estimates were pooled by a generic inverse variance random-effects meta-analysis model. The relative abundance of microbiome features was converted to log fold change, and the standard error was calculated from the p-values, sample size, and fold change. Results We screened 3874 potentially relevant publications. A total of 82 eligible studies comprising 37 autoimmune and 45 cancer studies with 4208 healthy human controls and 5957 disease cases from 27 countries were included in this study. We identified a set of microbiome features that show consistent, opposite directionality between cancers and autoimmune diseases in multiple studies. Fusobacterium and Peptostreptococcus were the most consistently increased genera among the cancer cases which were found to be associated in a remarkable 13 (+0.5 log fold change in 5 studies) and 11 studies (+3.6 log fold change in 5 studies), respectively. Conversely, Bacteroides was the most prominent genus, which was found to be increased in 12 autoimmune studies (+0.2 log fold change in 6 studies) and decreased in six cancer studies (−0.3 log fold change in 4 studies). Sulfur-metabolism pathways were found to be the most frequent pathways among the member of cancer-increased genus and species. Conclusions The surprising reproducibility of these associations across studies and geographies suggests a shared underlying mechanism shaping the microbiome across cancers and autoimmune diseases.

Chagas disease is related to structural changes of the gut microbiota in adults with chronic infection (TRIPOBIOME Study)

“…We found a significant enrichment of Parabacteroides spp among patients with Chagas disease. This genus has been associated with various diseases and conditions, including metabolic disorders, autoimmune diseases, and gastrointestinal disorders [ 63 , 64 ]. It is possible that Parabacteroides spp plays a role in modulating the immune response or altering the gut barrier function in Chagas disease patients.…”

Systems biology elucidates the distinctive metabolic niche filled by the human gut microbe Eggerthella lenta

“…The genes most strongly induced by treatment with agmatine were 2 copies of putrescine carbamoyltransferase, 1 copy of agmatine deiminase, and a transporter in the same operon (Fig 6D and S9 Table). Genes in the second complete agmatine deiminase operon (ELEN_RS110 [5][6][7][8][9][10][11][12][13][14][15]) were not differentially expressed, suggesting that the annotation of this second operon may be incorrect and/or may be involved in metabolism of a related compound. Interestingly, the most strongly down-regulated genes were 2 transport-related genes adjacent to the energy-conserving hydrogenase (Ech) complex (ELEN_RS078 [45][46][47][48][49][50]), one of which has structural homology to the arginineornithine antiporter found in the arginine deiminase operon (ELEN_RS09745, 27.6% identity).…”

Gut microbiome remains stable following COVID-19 vaccination in healthy and immuno-compromised individuals

“…Although our study cannot address long-term outgrowth of bacterial associated to these diseases, we are able to highlight if there is any temporal, acute changes in these species which is still of physiological relevance. Faecalibacterium prausnitzii, which is reported to be reduced in both gastric cancers, autoimmunity, and Crohn's disease 29 , showed no significant abundance changes at the vaccine timepoints in our cohorts [Fig2F].…”