gastrointestinal complaints – Page 2 – American ME and CFS Society

Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection

Abstract:

Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.

Source: Rizvi A, Ziv Y, Crawford JM, Trindade AJ. Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection. Gastroenterol Clin North Am. 2023 Mar;52(1):139-156. doi: 10.1016/j.gtc.2022.09.002. PMID: 36813422; PMCID: PMC9940919. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940919/ (Full text)

Investigating Immune Reactivity to the Intestinal Microbiome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) pathogenesis is thought to be multisystemic, including the immune and gastrointestinal systems. A proportion of patients experience gastrointestinal disturbances with evidence suggesting a leaky gut. It was hypothesised that a leaky gut and microbial translocation causes a breach in immune tolerance, promoting inflammation and autoimmunity.

Aims: A) determine whether severe ME/CFS patients have increased systemic and mucosal immunoglobulin (Ig) reactivity to the intestinal microbiome, and B) determine which intestinal microbes serum IgG was directed against.

Methods: Serum and stool samples were collected from five pairs of severe ME/CFS patients and matched household controls. Enzyme linked immunosorbent assays were developed to quantify IgG in serum, bound and non-bound IgA in stool and serum IgG levels reactive with autologous and heterologous stool bacteria. Flow cytometry methods were developed to quantify both stool microbial load and the proportion of stool microbes reactive with mucosal IgA and serum IgG. A ‘bug FACS’ method was developed to identify and quantify serum IgG reactivity to stool bacteria and fungi.

Results: The main finding was that severe ME/CFS patients have significantly lower levels of serum IgG reactive to heterologous stool bacteria compared to their matched household controls. In addition, severe ME/CFS patients do not have higher levels of serum IgG reactive to heterologous stool bacteria than autologous stool bacteria. Severe ME/CFS patients also have a non-significant increase of IgG binding to Campylobacter jejuni and Pseudomonas viridiflava compared to their matched household controls. Analysis of mucosal IgA found ME/CFS patients with a long disease duration had higher microbe bound IgA concentrations compared to their matched household controls.

Conclusion: This thesis presents results from the first ME/CFS study to investigate serum IgG immune reactivity to stool microbes. Findings suggest ME/CFS patients have an impaired serum IgG immune response to the intestinal microbiome.

Source: Seton, Katharine.  Investigating Immune Reactivity to the Intestinal Microbiome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Doctoral thesis, University of East Anglia. https://ueaeprints.uea.ac.uk/id/eprint/90862/

Gastric dysmotility and gastrointestinal symptoms in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Gastrointestinal symptoms are common in ME/CFS, but there is a knowledge gap in the literature concerning gastrointestinal motility features and detailed symptom description.

Objective: In this study, we aimed to characterize gastric motility and gastric symptoms in response to a liquid meal.

Methods: We included 20 patients with ME/CFS with abdominal complaints who were recruited to a double-blind randomized placebo-controlled trial of Rituximab. The patients of this sub study were examined with an ultrasound drink test, and gastrointestinal symptoms were evaluated using the Rome III questionnaire and Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) questionnaire.

Results: We found that patients commonly reported fullness/bloating (75%), abdominal pain (45%) and nausea (35%). Ultrasound measurements revealed lower proximal measurements of the stomach after a meal (p < 0.01) and larger fasting antral area (p = 0.019) compared to healthy controls. The patients had a stronger symptomatic response to the liquid meal compared to healthy controls regarding epigastric pain, discomfort and nausea (p < 0.05). Ninety percent of the patients reported bowel movement frequencies within the normal range but scored high on bowel habit dissatisfaction and life disruption.

Conclusion: The patients presented with fullness/bloating, nausea and epigastric pain, showed signs of impaired gastric accommodation and visceral hypersensitivity, showing that the gastrointestinal symptoms of ME/CFS patients are similar to functional dyspepsia.

Key summary:

Gastrointestinal symptoms are common in ME/CFS, but there is a knowledge gap in the literature concerning gastrointestinal motility features and detailed symptom description.
In this study, patients with ME/CFS had signs of impaired gastric accommodation after a liquid meal.
Out of 20 patients, 15 patients reported fullness/bloating, 9 reported abdominal pain, and 7 reported nausea. The patients showed signs of visceral hypersensitivity on a drink test.
Our findings suggest that patients with ME/CFS share many similarities with patients with Functional Dyspepsia. The findings were not typical for Irritable Bowel Syndrome.

Source: Steinsvik EK, Hausken T, Fluge Ø, Mella O, Gilja OH. Gastric dysmotility and gastrointestinal symptoms in myalgic encephalomyelitis/chronic fatigue syndrome. Scand J Gastroenterol. 2023 Feb 2:1-8. doi: 10.1080/00365521.2023.2173533. Epub ahead of print. PMID: 36728717. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0280942 (Full text)

Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review

Abstract:

Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia.

Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract.

In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection.

Source: Morello R, De Rose C, Cardinali S, Valentini P, Buonsenso D. Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review. Children. 2022; 9(10):1446. https://doi.org/10.3390/children9101446 (Full text)

Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis

Abstract:

Background: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic.

Objectives: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID.

Design: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed.

Data sources and methods: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages ‘meta’ and ‘metafor’.

Results: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06-0.22, I ² = 99%] and 0.22 (95% CI, 0.10-0.41, I ² = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04-0.38, I ² = 96%), 0.06 (95% CI, 0.03-0.11, I ² = 98%), 0.20 (95% CI, 0.08-0.43, I ² = 98%), and 0.17 (95% CI, 0.10-0.27, I ² = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04-0.23, I ² = 98%), 0.20 (95% CI, 0.06-0.50, I ² = 97%), and 0.17 (95% CI, 0.06-0.37, I ² = 96%), respectively.

Conclusion: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.

Source: Choudhury A, Tariq R, Jena A, Vesely EK, Singh S, Khanna S, Sharma V. Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis. Therap Adv Gastroenterol. 2022 Aug 19;15:17562848221118403. doi: 10.1177/17562848221118403. PMID: 36004306; PMCID: PMC9393939. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393939/ (Full text)

Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study

Abstract:

Background: Gastrointestinal infections represent a risk factor for functional gastrointestinal and somatoform extraintestinal disorders. We investigated the prevalence and relative risk (RR) of gastrointestinal and somatoform symptoms 5 months after SARS-CoV-2 infection compared with a control cohort.

Methods: One hundred and sixty-four SARS-CoV-2 infected patients and 183 controls responded to an online questionnaire about symptoms and signs during the acute phase of the infection and after 4.8 ± 0.3 months. Presence and severity of gastrointestinal symptoms, somatization, anxiety, and depression were recorded with standardized questionnaires. Stool form and presence of irritable bowel syndrome (IBS) were also recorded. Any association between exposure to infection and symptoms was evaluated by calculating crude and adjusted RR values and score differences with 95% confidence intervals (CI).

Key results: Fever, dyspnea, loss of smell/taste/weight, diarrhea, myalgia, arthralgia, and asthenia were reported by more than 40% of patients during the acute phase. Compared with controls, adjusted RRs for loose stools, chronic fatigue, and somatization were increased after infection: 1.88 (95% CI 0.99-3.54), 2.24 (95% CI 1.48-3.37), and 3.62 (95% CI 1.01-6.23), respectively. Gastrointestinal sequelae were greater in patients with diarrhea during the acute phase.

Conclusions & inferences: Mild gastroenterological symptoms persist 5 months after SARS-CoV-2 infection, in particular in patients reporting diarrhea in the acute phase. Infected patients are at increased risk of chronic fatigue and somatoform disorders, thus supporting the hypothesis that both functional gastrointestinal and somatoform disorders may have a common biological origin.

Source: Noviello D, Costantino A, Muscatello A, Bandera A, Consonni D, Vecchi M, Basilisco G. Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study. Neurogastroenterol Motil. 2022 Feb;34(2):e14187. doi: 10.1111/nmo.14187. Epub 2021 Jun 1. PMID: 34060710; PMCID: PMC8209890. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209890/ (Full text)

Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature

Abstract:

Eosinophilic colitis is a rare clinical condition that belongs to the group of eosinophilic gastrointestinal disorders. Its occurrence can be primary or secondary to infection, medications, or autoimmune/hematological conditions. We present a case of a young female adult with severe chronic fatigue syndrome, widespread chronic pain, including functional abdominal pain, who developed severe eosinophilic colitis following successive treatments with gabapentin and pregabalin. On both occasions, symptoms manifested as abdominal pain, diarrhea, and eosinophilia and improved upon discontinuation of the medications. Magnetic resonance imaging of the small bowel demonstrated an ascending colon colitis, and endoscopic investigations confirmed florid colitis mainly in the ascending colon with biopsies demonstrating a dense eosinophilic infiltrate with micro-abscesses. Serum eosinophil counts correlated well with the timing of the agents’ administration. There was no other organ involvement. Symptoms improved upon discontinuation of the drugs and steroid administration. Eosinophilic colitis is an exceptionally rare entity and its mechanism of action is still unclear. Suspicion of eosinophilic colitis should be raised if a patient presents with abdominal pain, diarrhea, and peripheral eosinophilia following treatment with pregabalin or gabapentin.

Source: Fragkos KC, Barragry J, Fernando CS, Novelli M, Begent J, Zárate-Lopez N. Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature. Z Gastroenterol. 2018 Jun;56(6):573-577. doi: 10.1055/a-0596-7981. Epub 2018 Jun 11. https://www.ncbi.nlm.nih.gov/pubmed/29890559

Cow’s milk protein intolerance in adolescents and young adults with chronic fatigue syndrome

Abstract:

AIM: To examine the prevalence, clinical features and influence on illness severity of cow’s milk protein intolerance in young people with chronic fatigue syndrome.

METHODS: In a two-year prospective study of 55 adolescents and young adults with chronic fatigue syndrome, we defined intolerance to milk protein if subjects reported (i) no evidence of immediate or anaphylactic reactions to milk, (ii) at least 2 of the following 3 chronic symptoms: gastroesophageal reflux, early satiety and epigastric/abdominal pain, (iii) improvement in upper gastrointestinal symptoms on a milk protein elimination diet and (iv) at least 2 recurrences of upper gastrointestinal symptoms >two hours following open re-exposure to milk protein. Subjects completed three quality of life surveys at baseline and at six months.

RESULTS: The mean (SD) age of the 55 participants was 16.5 (2.1) years. Seventeen (31%; 95% CI, 19-43%) met study criteria for cow’s milk protein intolerance. Compared to milk-tolerant subjects, milk-sensitive participants had significantly worse health-related quality of life at baseline but not at six months (after institution of the milk-free diet).

CONCLUSION: Cow’s milk protein intolerance is a common problem in young people with chronic fatigue syndrome and is a treatable contributor to their symptoms.

Source: Rowe PC, Marden CL, Jasion SE, Cranston EM, Flaherty MA, Kelly KJ. Cow’s milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8. doi: 10.1111/apa.13476. Epub 2016 Jun 3. https://www.ncbi.nlm.nih.gov/pubmed/27177188

Evidence for the existence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with and without abdominal discomfort (irritable bowel) syndrome

Abstract:

BACKGROUND: There is evidence that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is accompanied by gastro-intestinal symptoms; and IgA and IgM responses directed against lipopolysaccharides (LPS) of commensal bacteria, indicating bacterial translocation.

METHODS: This study was carried out to examine gastro-intestinal symptoms in subjects with ME/CFS versus those with chronic fatigue (CF). The two groups were dissected by dichotomizing those fulfilling and not fulfilling Fukuda’s critera. In these groups, we examined the association between gastro-intestinal symptoms and the IgA and IgM responses directed against commensal bacteria.

RESULTS: Using cluster analysis performed on gastro-intestinal symptoms we delineated that the cluster analysis-generated diagnosis of abdominal discomfort syndrome (ADS) was significantly higher in subjects with ME/CFS (59.6%) than in those with CF (17.7%). The diagnosis of ADS was strongly associated with the diagnosis of irritable bowel syndrome (IBS). There is evidence that ME/CFS consists of two subgroups, i.e. ME/CFS with and without ADS. Factor analysis showed four factors, i.e. 1) inflammation-hyperalgesia; 2) fatigue-malaise; 3) gastro-intestinal symptoms/ADS; and 4) neurocognitive symptoms. The IgA and IgM responses to LPS of commensal bacteria were significantly higher in ME/CFS patients with ADS than in those without ADS.

CONCLUSIONS: The findings show that ADS is a characteristic of a subset of patients with ME/CFS and that increased bacterial translocation (leaky gut) is associated with ADS symptoms. This study has defined a pathway phenotype, i.e bacterial translocation, that is related to ME/CFS and ADS/IBS and that may drive systemic inflammatory processes.

Source: Maes M, Leunis JC, Geffard M, Berk M. Evidence for the existence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with and without abdominal discomfort (irritable bowel) syndrome. Neuro Endocrinol Lett. 2014;35(6):445-53. https://www.ncbi.nlm.nih.gov/pubmed/25433843

Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins

Abstract:

Myalgic encephalomyelitis (ME) is a debilitating illness of unknown etiology characterized by neurocognitive dysfunction, inflammation, immune abnormalities and gastrointestinal distress. An increasing body of evidence suggests that disruptions in the gut may contribute to the induction of neuroinflammation. Therefore, reports of human endogenous retroviral (HERV) expression in association with neuroinflammatory diseases prompted us to investigate the gut of individuals with ME for the presence of HERV proteins.

In eight out of 12 individuals with ME, immunoreactivity to HERV proteins was observed in duodenal biopsies. In contrast, no immunoreactivity was detected in any of the eight controls. Immunoreactivity to HERV Gag and Env proteins was uniquely co-localized in hematopoietic cells expressing the C-type lectin receptor CLEC4C (CD303/BDCA2), the co-stimulatory marker CD86 and the class II major histocompatibility complex HLA-DR, consistent with plasmacytoid dendritic cells (pDCs). Although the significance of HERVs present in the pDCs of individuals with ME has yet to be determined, these data raise the possibility of an involvment of pDCs and HERVs in ME pathology. To our knowledge, this report describes the first direct association between pDCs and HERVs in human disease.

Source: De Meirleir KL, Khaiboullina SF, Frémont M, Hulstaert J, Rizvanov AA, Palotás A, Lombardi VC. Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins. In Vivo. 2013 Mar-Apr;27(2):177-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776582/ (Full article)