ABSTRACT
This review is aimed to explore the health beneficial effects of probiotics which are live microorganisms that provide a positive health influence on humans when taken in sufficient quantity. Lactic acid bacteria, bifidobacteria, and yeast are frequently used as probiotics. These health-beneficial bacteria could compete with pathogens and modulate the gut microbiota, and exhibit immunomodulatory, anti-obesity, anti-diabetic, and anti-cancer activities which are discussed in this review. Moreover, recent studies showed that probiotics could neutralize COVID-19 infections. Hence, probiotics have become an alternative to several drugs including antibiotics. In addition, probiotic efficacy also depends on the delivery system as the delivery agents help the bacteria to survive in the harsh environment of the human gut. Considering these health benefits of probiotics, now it has been applied to different food materials which are designated as functional food. This review explored a portrait of the beneficial effects of probiotics on human health.Copyright © 2022 The Author(s)
ABSTRACT
Background: Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (GI) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, in-vitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SARS-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19. Methods: Individuals with previous COVID-19 diagnosis (by either RT–PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells) and NK cells. Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody. Results: Thirty subjects with a previous history of COVID-19 (post-COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC)1 (lin-HLA-DRhiCD14- CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14-CD11c+CD1c+) were noted in the colon. Among NK subsets, CD56bright CD16- NK cells were significantly higher in the colon of post-COVID subjects. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p= 0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). Conclusion: Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long-term sequelae of COVID-19, including long-haul COVID.(Table Presented)(Figure Presented)
ABSTRACT
Background: Although SARS-CoV-2 has mainly respiratory manifestations, gastrointestinal symptoms are observed in 30% of cases. The ACE-2 receptor used by SARS-CoV-2 to infect cells is highly expressed in the brush border of enterocytes. However, studying the small intestine in live patients is a challenge in the field of clinical research. A minimally invasive alternative for studying the small intestine is the use of capsule endoscopy, which could be useful in the context of COVID-19. Here, we describe endoscopic changes in the mucosa of the small intestine secondary to severe SARS-CoV-2 infection in hospitalized patients. Methods: We performed a prospective observational study in hospitalized patients with a severe COVID-19 according to NIH guidelines. Participants with a positive COVID-19 PCR from nasopharyngeal swab, hemodynamically stable, able to swallow, and without additional respiratory co-infections, were enrolled between January 27th and May 17th, 2021 at the largest tertiary COVID-19 referral center in Mexico City. Demographic and clinical characteristics were collected for each participant from clinical files. A PillCam capsule from Medtronic® was used for Capsule Endoscopy (CE). Each capsule study was reviewed separately by two trained endoscopists. Detection of SARS-CoV-2 RNA in stool samples was performed according to CDC guidelines for all participants. Results: Twenty volunteers were enrolled in the study. Diarrhea was the most common gastrointestinal symptom (78%). CE study was normal in 6 participants, while the rest showed at least one intestinal finding. The most frequent finding was shortening or atrophy of villi and hyperemia (45%);followed by red spots (40%), and ulcers (15%). Two participants with shortening or atrophy of villi also presented denuded mucosa. CE findings were observed mainly in duodenum and jejunum. Participants showing changes in villi also presented positive SARS-CoV-2 RNA in stool. Conclusion: We observed that macroscopic changes in the small intestine mucosa, specifically in villi, occurred frequently in severe COVID-19 patients. These changes were accompanied by the presence of SARS-CoV-2 RNA in stool. We proposed the term COVID-19 Enteropathy to encompass these findings. Further studies are warranted to establish mechanisms of SARS-CoV-2-associated gastrointestinal disease.
ABSTRACT
Background: Gastrointestinal symptoms and viral RNA (vRNA) in stool have been described in human SARS-CoV-2 infections. However, intestinal pathology and related inflammation have not been extensively described in humans or animal models. Here we investigate the effect of SARS-CoV-2 infection on the gut mucosa and inflammation in rhesus macaques (RM) and humans. Methods: Fourteen adult RM were infected with US/WA-1/2020 SARS-CoV-2 instilled intranasally and intratracheally. Animal clinical features (mass, temperature, etc.) and samples (nasal swabs, throat swabs, blood, stool, etc.) were collected at baseline and up to day 10 post-infection at necropsy. RNA was extracted from swab and stool samples and vRNA measured by qRT-PCR. Plasma samples were assessed for inflammatory biomarkers by ELISA. Tissues collected at necropsy were fixed and evaluated for microbial translocation through immunohistochemical (IHC) staining of bacterial products;H&E staining was also performed. Tissues were additionally collected from uninfected RM and processed in the same manner. Human plasma samples from individuals with moderate COVID-19 were collected at early infection and recovery time points and assessed for inflammatory biomarkers. Results: SARS-CoV-2 infection of RM did not induce fever nor weight loss over five percent. vRNA was detected in all animals in nasal and throat swabs. vRNA, including subgenomic RNA indicative of viral replication, was also detected in stool samples. Scores for translocating bacteria in colon sections stained by IHC for bacterial products were higher for SARS-CoV-2 infected RM than uninfected controls. Additionally, follicles made up a higher percentage of total mesenteric lymph node area in SARS-CoV-2 infected animals than control RM. Furthermore, soluble CD14 in plasma increased significantly from baseline to day 10 of SARS-CoV-2 infection (p=0.0006) and decreased significantly in humans from early infection to recovery time points (p=0.0295). Conclusion: Thus, adult RM experienced mild to moderate SARS-CoV-2 infections yet demonstrated evidence of microbial translocation. Humans similarly demonstrated evidence of microbial translocation that decreased upon recovery from COVID-19. These data suggest gut pathology in SARS-CoV-2 infection may be contributing to systemic inflammation in COVID-19.
ABSTRACT
Background: Although respiratory failure is the hallmark of severe disease, it is increasingly clear that Coronavirus Disease 2019 (COVID-19) is a multi-system disorder. The presence of gastrointestinal (Gl) involvement by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suggested by epidemiological, clinical, non-human primate, invitro (enteroid) and ex-vivo (human biopsy) studies. Having recently documented persistence of SAR-CoV-2 within the intestinal epithelium 7 months after infection, here we aimed to study mucosal immune cell abnormalities in individuals with prior history of COVID-19. Methods: Individuals with previous COVID-19 diagnosis (by either RT- PCR or seroconversion) and controls (without RT-PCR or serological evidence of prior COVID-19 infection) undergoing endoscopic evaluation were recruited into the study (Table 1,2). Colonic and small intestinal (duodenal and ileal) biopsies were analyzed by multiparameter flow cytometry for mucosal immune cell populations including myeloid cells (classical and non-classical monocytes, dendritic cell subsets), T cells (subsets and activation state), B cells (including plasma cells). Persistence of viral antigens was determined by immunofluorescence microscopy (n=30) using a previously published anti-nucleocapsid (NP) antibody. Results: Thirty subjects with a previous history of COVID-19 (post- COVID), median of 4 months from diagnosis (range 1-10 months), were recruited and compared with 40 normal volunteer (NV) controls. Relative to controls, post-COVID subjects displayed higher frequencies of classical (CD14+) monocytes in both, the colon and the small bowel, while significantly higher frequencies of conventional dendritic cells (cDC) 1 (lin-HLA-DRhiCD14-CD11c+CD141+) and cDC2 (lin-HLA-DRhiCD14-- CD11c+CD1c+) were noted in the colon only. Among T cell subsets, CD8+ tissue resident memory T cells (CD8+CD69+CD103+) were significantly increased in colon of post-COVID subjects compared to NV. Among B cell subsets, plasma cells (CD3-CD27+CD38hi) trended higher (p=0.06), while mucosal B cells (CD3-CD19+) were significantly lower in the terminal ileum of post-COVID subjects compared to NV. Finally, with IF, we detected SARS-CoV-2 NP in 10 out of 30 (33%) of post-COVID subjects (Figure 1). There were no significant correlations of these cell populations with either time after the infection or IF positivity. Conclusion: Innate and adaptive immune cell abnormalities persist in the intestinal mucosa of post-COVID subjects for up to 10 months and may reflect viral persistence or immune cell dysregulation in the intestines. These findings have major implications for understanding the pathogenesis of long term sequela of COVID-19, including long-haul COVID.