Wednesday, January 20, 2021

Irritable Bowel and COVID-19

The first symptoms of Coronavirus disease  (day 0) begin from two to 14 days after exposure to the virus (marked as day –5 in the figure below, since median time is about five days). The disease affects
different people in different ways. A recent article identified 6 distinct types of COVID-19 with different symptoms,  some of which are hallmarks of the most severe forms of the disease. SARS-CoV-2-infected patients usually first experience a fever. The fever is often followed by a dry cough or fatigue and muscle pain, followed by GI tract symptoms, if they ever occur. Some people, experience nausea or have diarrhea in the days just before the fever begins. 

Gastrointestinal symptoms are reported in about one third of COVID-19 cases, the most common is loss of appetite  - it can happen even in the mildest form of the disease. Nausea/vomiting and diarrhea are slightly less common. Abdominal pain is even less widely known in COVID-19, yet it is  - along with shortness of breath and confusion - is a potential sign of the most severe form of COVID-19. In children, having gastrointestinal symptoms was more frequently associated with severe and critical phenotype (Giacomet et al, 2020). Hyperinflammatory syndrome was presenting with both cardiac and significant GI symptoms (diarrhea, vomit, abdominal pain).

Some researchers suggest that gut dysfunction may exacerbate the severity of infection by enabling the virus to access the surface of the digestive tract and internal organs. These organs are vulnerable to infection because they have widespread ACE2—a protein target of SARS-CoV-2 for its possible routes of entry —on the surface.  ACE2 is abundantly present in the epithelia of the lung and small intestine.

Yet, even if SARS-CoV-2 reaches the GI tract, it may not cause GI problems. An inflamed leaky gut, however, may be associated with a higher risk of severe illness and the microbial imbalance of the gut affecting gut barrier integrity can allow pathogens and pathobionts easier access to cells in the intestinal lining.

Several studies have already demonstrated that, when compared with healthy individuals, COVID-19 patients present a significantly reduced bacterial diversity and higher abundancy of opportunistic Streptococcus, Rothia, Veilonella, and Actinomyces compared to depleted levels of beneficial Agathobacter, Fusicatenibacter, Roseburia, and Ruminococcaceae UCG-013. Rothia was preeviously thought to contribute to the pathogenesis of pneumonia. Critically ill patients on mechanical ventilation who were given probiotics experienced decrease in viral colonization when compared with placebo. However, the efficacy of probiotics use in COVID-19 patients and other bowel remedies remains to be proved.


REFERENES

La Marca A, Capuzzo M, Paglia T, Roli L, Trenti T, Nelson SM. Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays. Reproductive biomedicine online. 2020 Jun 14.

Oshima T, Siah KT, Yoshimoto T, Miura K, Tomita T, Fukui H, Miwa H. Impacts of the COVID‐19 pandemic on functional dyspepsia and irritable bowel syndrome: A population‐based survey. Journal of gastroenterology and hepatology. 2020 Nov 16.

Sudre CH, Lee KA, Lochlainn MN, Varsavsky T, Murray B, Graham MS, Menni C, Modat M, Bowyer RC, Nguyen LH, Drew DA. Symptom clusters in Covid19: A potential clinical prediction tool from the COVID Symptom study app. MedRxiv. 2020 Jan 1.

Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–1608.

Giacomet V, Barcellini L, Stracuzzi M, Longoni E, Folgori L, Leone A, Zuccotti GV. Gastrointestinal Symptoms in Severe COVID-19 Children. The Pediatric infectious disease journal. 2020 Aug 10;39(10):e317-20.

Cholankeril G, Podboy A, Aivaliotis VI, Tarlow B, Pham EA, Spencer SP, Kim D, Hsing A, Ahmed A. High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California. Gastroenterology. 2020 Aug 1;159(2):775-7.

Gu, S.; Chen, Y.; Wu, Z.; Chen, Y.; Gao, H.; Lv, L.; Guo, F.; Zhang, X.; Luo, R.; Huang, C.; et al. Alterations of the Gut Microbiota in Patients with COVID-19 or H1N1 Influenza. Clin. Infect. Dis. 2020, 71, 2669–2678.

Dhar, D.; Mohanty, A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020, 285, 198018. 

Sudre CH, Lee KA, Lochlainn MN, Varsavsky T, Murray B, Graham MS, Menni C, Modat M, Bowyer RC, Nguyen LH, Drew DA. Symptom clusters in Covid19: A potential clinical prediction tool from the COVID Symptom study app. MedRxiv. 2020, June 16. 


Ferreira, C.; Viana, S.D.; Reis, F. Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update. Microorganisms 2021, 9, 53.

Wednesday, September 30, 2020

Microbiome-based strategies for IBS

 There is evidence that the microbiome is implicated in the pathogenesis of irritable bowel syndrome (IBS), or associated with it in one way or another. Many patients can trace their symptom onset back to infectious gastroenteritis or multiple courses of antibiotics.  Microbiome-based strategies (eg, probiotics, diet, antibiotics) offer benefits to subsets of patients and so does the use of fecal microbiota transplantation (FMT).

Development of microbiome-directed medicine is stalled by the laborious nature of conventional cultivation methods and insufficient data for machine learning-driven approaches. Read more ...

Friday, November 18, 2016

Who is afraid of IBS?

Irritable bowel syndrome, also known as IBS, used to be a rare condition, but - due to industrialization and urbanization - it is now one of the most common disorders in the world. The term is even used figuratively, in a derogatory sense.

The numbers of new reported cases of irritable bowel syndrome kept increasing into the 21st century when they reached almost epidemic proportions. As the amount of information available on the Internet exploded, so did the web searches about IBS.  But then the disorder "came out of the closet", and google searches for "irritable bowel syndrome" started to dwindle, reaching a quarter of what they used to be at the peak. This downtrend mirrored ambulatory data (National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey) showing that by 2010, the rate of IBS-related visits decreased roughly by 37%.

Is IBS no longer a problem?

Sunday, May 10, 2015

Making Digestion Health Easier to Digest

From balloons inserted into stomach or colon to the dreaded colonoscopy, digestive diagnostic procedures are not fun. Tracking diet and symptoms, too, is tedious and frustrating - unless, like a mouse, you can be isolated in a chamber linked to analyzers that automatically measure everything for you.

New noninvasive tests are emerging but adoption is slow. Medicare and most insurance plans won’t pay for a less invasive version of the conventional colonoscopy - CT colonography  - as its lacks the sensitivity and specificity of the traditional test.
Pill cameras for the detection of colorectal polyps and cancer are, too, still inferior to those of standard colonoscopy. Besides, even though these tests are much faster and less invasive than conventional techniques, patients still need a cleansing preparation of their bowel prior to the test. In addition, the pill camera that usually exits the body after 10 hours, has to be surgically removed in 8% of the patients. And virtual colonoscopy leads to more “incidentalomas" and unnecessary treatments.  A few novel endoscopic innovations also have uncertain clinical relevance.

A simple wearable tracker of intestinal gas recently proposed by a Brazilian designer and telecommunications major  does not seem to attract much interest in consumers. Perhaps it is because it offers too little information? After all, even the cow health tracker - Well Cow pill - measures not only the gas-forming potential of foods, but also pH and temperature within the digestive system to better monitor the healthiness of diet.


Accurate measurement of intestinal gases could offer new insights into lives of human gut microbes and metabolic activities.  Two novel techniques, in vitro fermentation and swallowable gas capsule systems, for measuring and assessing selected gas species, were recently proposed and could potentially be used for less invasive diagnostics of irritable bowel syndrome, inflammatory bowel disease, colon cancer, and other gastrointestinal conditions. But could not we do better than popping gas sensor "pills" for easy every-day measurements of digestive health?

We at Aurametrix think so. Stay tuned for more. 


REFERENCES

Ou JZ, Yao CK, Rotbart A, Muir JG, Gibson PR, & Kalantar-Zadeh K (2015). Human intestinal gas measurement systems: in vitro fermentation and gas capsules. Trends in biotechnology, 33 (4), 208-213 PMID: 25772639

Speakman, J. (2013). Measuring Energy Metabolism in the Mouse – Theoretical, Practical, and Analytical Considerations Frontiers in Physiology, 4 DOI: 10.3389/fphys.2013.00034

von Delius S, Schmid RM, & Meining A (2010). Pill camera. Endoscopy, 42 Suppl 2 PMID: 20556714

Monday, November 10, 2014

Intestinal Parasites: Friends, Foes and Shades of Gray


Parasite is a bad word with negative connotations. Yet, "bad things" can be good for you - and every situation is different.

About one third of people in the world carry at least one parasite in their gastrointestinal tract (the numbers reported vary from 2-4% in Japanese residing in developing countries to 6% in patients of a specialized private hospital in Saudi Arabia, 7% among individuals with mental retardation in New York, 17% in HIV patients with low CD4 counts in France, 30% in households of USA, Saudi Arabia and Turkey, 40% in Pakistan and Brasil, to over 50% in Nigeria, 50-70% in Morocco and almost 100% in Senegal). Prevalence varies between countries and within communities. Women and children appear to harbor larger numbers of parasites. But men, in general, may be less healthy than women, so the relationship between health and intestinal parasites is not as straightforward as one might think.

Let's take a look at three studies published this year.

Paper by Lukeš and co-authors (2014) suggests that intestinal parasites such as Blastocystis (single celled protozoa closely related to algae and molds) and nematodes (e.g., tapeworms or hookworms) can be actually beneficial to human health. To prove the point, Julius Lukeš even ingested  a handful of tapeworms called Diphyllobothrium latum. After more than a year with the tapeworms, which might have grown to be as long as four meters each by now, he still feels healthy and convinced that we should rethink our views of organisms that live off our bodies.

According to a Danish study (Krogsgaard et al, 2014), Blastocystis could be rare in individuals with low microbial diversity, disturbed by antibiotic treatment, inflammation, infection and diet, while common in the healthy population. Healthy individuals are more likely to carry intestinal parasites (50% vs 36%) than those with IBS and IBD. Protozoa Blastocystis and Dientamoeba were the most common parasites found. D fragilis was detected in a greater proportion of fecal samples from controls than cases (35% vs 23%; P = .03), and so was Blastocystis (22% of controls vs 15% of cases; P = .09), and combinations of parasite species (16% of controls vs 8% of cases; P = .05). D fragilis infection was more likely among those with low frequency of defecation and those having children 5 to 18 years old in the household. Blastocystis was associated with high income, increasing age, no animals in the household and drinking bottled water. These results are drawn from analyzing hundreds of individuals - 124 cases/204 controls.

Smaller and more focused studies, however, do find association between Blastocystis and IBS.

A recent French study compared the prevalence of Blastocystis among 56 IBS patients and  56 control and found that Blastocystis species are likely to couse IBS symptoms in men (prevalence was 37% in IBS sufferers vs 5% in healthy men; difference in women was not statistically significant). One of the older smaller studies that indicated possible relation between Blastocytes and IBS (Funda Dogruman-Al et al., 2009) suggested that Blastocystis don't really attack the body, it's the human organism that attacks the microbes first and the outcome is the result of defensive actions by the microbes. Obviously, symptoms do depend on many other health factors. Nourrisson and co-authors identified them as the prevalence of certain "good" bacteria. Men are more likely to get constipated when their Blastocystis leads to a significant decrease in Bifidobacterium species. On the other hand, they are doing just fine if Blastocystis causes decrease in Faecalibacterium prausnitzii - relatively good bacteria known for its anti-inflammatory properties,

Another interesting insight into the impact of a complex interplay of environmental factors on our health. Still a long way to go to understand how we interact with microbes that call us home.


REFERENCES

Lukeš J, Kuchta R, Scholz T, & Pomajbíková K (2014). (Self-) infections with parasites: re-interpretations for the present. Trends in parasitology, 30 (8), 377-85 PMID: 25033775
press release

Krogsgaard LR, Engsbro AL, Stensvold CR, Nielsen HV, & Bytzer P (2014). The Prevalence of Intestinal Parasites Is Not Greater Among Individuals With Irritable Bowel Syndrome: a Population-Based Case-Control Study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association PMID: 25229421

Nourrisson C, Scanzi J, Pereira B, NkoudMongo C, Wawrzyniak I, Cian A, Viscogliosi E, Livrelli V, Delbac F, Dapoigny M, & Poirier P (2014). Blastocystis Is Associated with Decrease of Fecal Microbiota Protective Bacteria: Comparative Analysis between Patients with Irritable Bowel Syndrome and Control Subjects. PloS one, 9 (11) PMID: 25365580

El Safadi D, Gaayeb L, Meloni D, Cian A, Poirier P, et al. (2014) Children of Senegal River Basin show the highest prevalence of Blastocystis sp. ever observed worldwide. BMC Infect Dis 14: 164 doi:10.1186/1471-2334-14-164.

Boorom KF, Smith H, Nimri L, Viscogliosi E, Spanakos G, Parkar U, Li LH, Zhou XN, Ok UZ, Leelayoova S, Jones MS: (2008) Oh my aching gut: irritable bowel syndrome, Blastocystis, and asymptomatic infection. Parasit Vectors, 1:40 2

Krogsgaard LR, Engsbro AL, & Bytzer P (2013). The epidemiology of irritable bowel syndrome in Denmark. A population-based survey in adults ≤50 years of age. Scandinavian Journal of Gastroenterology, 48 (5), 523-9 PMID: 23506174

(2004) Intestinal parasites prevalence and related factors in school children, a western city sample--Turkey. BMC Public Health. 2004 Dec 22;4:64.

Houmsou R.S., Amuta E.U., Olusi T.A. (2010) Prevalence of intestinal parasites among primary school children in Makurdi, Benue State- Nigeria. Internet Journal of Infectious Diseaes. vol.8, 1, p.2

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Sah, Ram; Bhattarai, Sailesh; Yadav, Satish; Baral, Ratna; Nilambar; Pokharel, Paras (2013) A study of prevalence of intestinal parasites and associated risk factors among the school children of Itahari, Eastern Region of Nepal. Tropical Parasitology, 3, 2, 140-144, DOI 10.4103/2229-5070.122143

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Jeevitha Dhanabal, Pradeep Pushparaj Selvadoss, and Kanchana Muthuswamy (2014) Comparative Study of the Prevalence of Intestinal Parasites in Low Socioeconomic Areas from South Chennai, India. Journal of Parasitology Research Volume 2014 (2014), Article ID 630968, 7 pages http://dx.doi.org/10.1155/2014/630968

Blagburn BL1, Schenker R, Gagne F, Drake J.(2008) Vet Ther. 2008 Fall;9(3):169-75. Prevalence of intestinal parasites in companion animals in Ontario and Quebec, Canada, during the winter months.

Hamada A1, Okuzawa E, Kawabuchi Y, Nishikawa T. (1998) Kansenshogaku Zasshi. 1998 Dec;72(12):1283-8. [Prevalence of intestinal parasites among Japanese residents in developing countries]. [Article in Japanese]

Hirata, T., Nakamura, H., Kinjo, N., Hokama, A., Kinjo, F., Yamane, N. et al. (2007) Prevalence of Blastocystis hominis and Strongyloides stercoralis infection in Okinawa, Japan. Parasitol Res 101: 17171719.

Javed Yakoob, Wasim Jafri, Nadim Jafri, Rustam Khan, Muhammad Islam, M. Asim Beg, and Viqar Zaman (2004) Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis Am. J. Trop. Med. Hyg., 70(4), pp. 383–385