Alterations in the human oral and gut microbiomes and lipidomics in COVID-19

Abstract

ObjectiveTo characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile.DesignWe collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity.ResultsOral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery.ConclusionThis study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19

“…COVD-negative cases in our study also have ground glass opacity in the lung that may be viral pneumonia caused by other kinds of viruses. Several 16S rRNA gene sequencing studies had showed the alterations in the human oral and upper respiratory microbiomes in COVID-19 [ 25 , 26 ]. Recently, a Chinese team from Wuhan institute of virology published a metagenomic sequencing study that reveals the potential linkages between pharyngeal microbiota and COVID-19 [ 15 ].…”

Do Gut Microbes Taste?

“…This results in local inflammation, disruption in resident microbiota and gut barrier dysfunction, thus decreasing secretion of antimicrobial peptides and facilitating bacterial metabolomes and byproducts to enter the circulation leading to systemic inflammation [ 122 , 123 , 124 ]. Several studies have shown that patients with COVID-19 have an altered microbiome characterized by an overall decline in microbial diversity, enrichment of opportunistic pathogens Clostridium hathewayi, Actinomyces viscosus, Bacteroides nordii, Streptococcus, Rothia, Erysipelatoclostridium and Veillonella along with significant depletion of beneficial commensals such as Lachnospiraceae bacterium , Eubacterium rectale , Ruminococcus obeum , Fusicatenibacter , Eubacterium hallii , Anaerostipes , Agathobacter , Roseburia , Dorea formicigenerans , Clostridium butyricum , Clostridium leptum and Faecalibacterium prausnitzii [ 125 , 126 ]. Some of these beneficial bacteria which includes butyric acid producing bacteria have been linked to reduced inflammation.…”

“…In fact, abundance of certain gut bacteria such as Coprobacillus , Clostridium ramosum and Clostridium hathewayi , correlated with COVID-19 severity. Taste sensitivity is reduced in inflammatory conditions [ 126 ]; however, the contribution of systemic inflammation to taste changes in the oral cavity is not known. It is interesting to note that, Type II cells “taste” amino acids and ACE2 in the gut is involved in amino acid absorption [ 130 ].…”

“…Indeed, bariatric procedures, such as Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG), results in significant changes in the anatomy, function, diet and intraluminal milieu of the gastrointestinal tract affecting the gut microbiota [ 143 , 144 ]. Gut microbiota plays a key role in pathogenesis of obesity and obesity has been characterized by a dysbiotic microbiota, with differences in both salivary and fecal microbiota composition profile and bacterially derived metabolites such as γ-amino butyric acid and butyrate between obese and normal weight individuals [ 126 ]. Changes in the gut microbiota composition profile are rapid, as early as one week after surgery, and are due to multiple factors including changes in diet, antibiotic treatment, anatomical reconfiguration of the gastrointestinal tract and weight loss.…”

Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection

“…The potential for diagnostic markers that can better stratify patient response to infection is highlighted in reports that indicated higher levels of diglycerides (DAGs), free fatty acids (FFAs), and triglycerides (TAGs) in fatal cases of COVID-19, and that abundance was correlated with deterioration of the disease [ 25 ]. However, the requirement for the validation of lipid biomarkers in multiple independent cohorts is highlighted by conflicted reports on phospholipid changes, with increases in phosphocholines (PCs) and phosphoethanolamines (PEs) reported [ 12 , 26 ], as well as significant downregulation [ 23 ]. Furthermore, Song et al identified decreases in longer chain TAGs and DAGs [ 27 ], in contrast to the previously discussed studies.…”