A probiotic product has recently received some media attention for treatment of symptoms following COVID. Several clients have now asked me whether I am prescribing it in my Microbiome Analysis practice, so I decided I would write a blog about the trial, some findings of my work with Long Covid clients and related treatment decisions.
IMAGE: Viola's hand holding a probiotic capsule in an open palm.
A team at Bedford Hospital conducted an experimental trial of the probiotic YourGutPlus, to assess its potential in the treatment of post-COVID symptoms. It was led by Dr Robert Thomas, a cancer specialist who recently published a book on lifestyle choices to support health, including some dietary tips related to the gut microbiome.
This is the first trial of these probiotic strains
The probiotic product contains five bacterial strains in a capsule with a very small amount of prebiotic inulin (this is known as a synbiotic). When I first heard about the trial shortly after it started in 2020, I asked YourGutPlus for the bacterial strain details, as they only list the species on their website and packaging. But they were unable to provide those details to me, so I was unable to do the research into the strains that I'd need to, to consider it in my Microbiome Analysis practice.
I was excited to hear of the Bedford Hospital trial when listening to Dr Thomas in an interview promoting his new book in September 2020, and so I was pleased to be able to read the results when it was published in the open access journal of Infectious Diseases Diagnosis and Treatment.
This paper lists the strains within the synbiotic as: Lactobacillus plantarum LP-90; Lactobacillus rhamnosus LRa05; Lactobacillus bulgaricus LB42; Lactococcus lactis La61 and Lactobacillus paracasei LC86, which do not have any previous clinical trial data showing they have any beneficial action. The paper says the research team selected these bacterial strains specifically for the trial, and I would be very interested to understand what properties they chose them for, in absence of information on their probiotic action.
Results sound promising, despite weaknesses in study design
This experimental trial was relatively small, involving 40 people who had symptoms within the 30 days prior to the start of the trial (ie recent COVID infection), and 86 who had symptoms persisting longer than 30 days. In the latter group, the average time of symptoms was 120 days, meaning only some of those participants would be diagnosed with Long Covid, ie illness longer than 120 days. Each of the 126 patients was given 1 capsule of the synbiotic daily, over a study period of 30 days.
The results sound promising, despite there being some weaknesses in the study design, in addition to the small number of participants. It was unfortunately not a double-blinded, randomised controlled trial – the kind of trial that gives us the most robust evidence. There was no control group (as the research team decided that people would want to purchase probiotics themselves), so we can’t rule out the placebo effect – especially important given the popularity of probiotics. I recall from the interview with Dr Thomas that participants were eager to join the trial as they'd heard about the benefits of probiotics to our health, and this may have raised ethical considerations about a control group.
The lack of control group also means we can’t see whether the results would have been similar to a group that had no treatment, or not. With so many of the patients having had post-Covid symptoms for less than 120 days, we’d expect a high proportion of those to experience improvement in symptoms, with or without a probiotic.
Patients reported some improvement in some symptoms
It is good practice in clinical trials to use validated instruments to record symptom changes, and this trial used the validated Cough Symptom Score, Subjective Well-Being questionnaire and the Chandler fatigue questionnaire. Using these, participants recorded their symptoms at the start of the trial and on the 30th day. We know post-Covid symptoms can fluctuate on a daily basis, so additional symptom tracking would have been ideal, but the very short treatment window of 30 days may not have made that much more meaningful.
117 of the 126 participants reported fatigue symptoms at the start of the trial, while 31 reported coughing. The researchers reported statistically-significant improvements in scores for fatigue, cough and subjective wellbeing across the two patient groups at 30 days. They also concluded that participants who were statistically more likely to have gut dysbiosis (disrupted microbiome) at trial entry, such as sedentary, hospitalised, older males with digestive symptoms, had a significantly better response to the probiotics.
The most common symptoms at the start of the trial were: fatigue 117 patients (92% of the 126 recruited); breathlessness 53 (42%); joint, muscle or chest pains 43 (34%); cough 31 (25%); altered sense of smell 31 (25%); and bowel symptoms or nausea 31 (25%). Only 8 of the 126 participants had brain fog, which is one of the most common symptoms of Long Covid. Of these 8 people, 3 reported some improvement after 30 days of taking the probiotic.
Of the 31 people with bowel symptoms, 25 reported some improvements in those symptoms, while 11 out of the 53 who had breathlessness reported some improvement, but the trial published data does not tell us whether these were completely resolved for any of them in that time. 8 reported palpitations at the start of the trial, with 1 person reporting some improvement in those after 30 days.
Other symptoms that showed some improvements were joint or chest pains, sleep, headache, asthma, skin oiliness and sneezing, with between 1 and 8 of the 126 patients reporting a reduction in severity in one or more of those symptoms. Two participants dropped out of the trial due to digestive discomfort (bloating and diarrhoea), which may not have been due to the synbiotic, although inulin often causes bloating, especially in people whose microbiome is severely disrupted.
The trial results echo my clinical experience
The trial period was only 30 days and the results correspond with my experience working with Long Covid clients. Symptoms such as fatigue and brain fog usually show some improvement quite quickly (within the first few weeks), as do any digestive issues, which are common in this client group. However major improvements, or complete resolution of symptoms, usually takes several months. Certain symptoms, such as palpitations and chest pain, respond to microbiome interventions much more slowly. Full recovery can take at least 6 months of following a programme of targeted prebiotics, probiotics and food changes, tailored to each individual's microbiome and continuously developed according to their progress. For some, it is taking much longer.
I’ve found that people seeking Microbiome Analysis sooner after their Long Covid diagnosis have recovered faster. This may be due to earlier treatment or perhaps the later COVID variants, or wider awareness of the risk of Long Covid and the need to take convalescence more seriously following COVID. There are a few clients who I have now been working with for more than one year, all of whom became ill in 2020, and while they have all reported significant improvement in symptoms, there is still some way to go.
Microbiome restoration is often a slow process as the gut ecosystem takes time to adapt. But as a general trend, I am finding that although clients with Long Covid feel some benefit from microbiome interventions early on, they need much higher doses of prebiotics and longer treatment plans than other conditions, before follow-up testing shows corresponding changes in their microbiome. This raises some important questions about gut microbiome resilience, or even perhaps viral persistence in the gut, as potential factors in the development of Long Covid.
I prescribe probiotics that have robust clinical evidence
Good clinical trials are costly, making probiotic strains with robust trial data more expensive for companies sourcing strains for their products. Unfortunately this means the majority of probiotic formulae available on the high street do not have any clinical trials backing up their manufacturers' claims, and food labelling laws do not require them. Those that do have good clinical data, tend to list the strain details proudly on their labels. (Strain details are usually letters or numbers after the two-part species name, such as Bifidobacterium lactis HN019 or Lactiplantibacillus plantarum 299v. For more on the importance of strain specificity in choosing probiotics, please see my earlier blog.)
I have now searched for previously published clinical trial data for each of the strains used in YourGutPlus, and have found none, although one has been studied in lab mice. I also asked the company several times over the past 18 months for clinical trial data for any of its strains, singly or in combination, but they have not been able to provide me with any. According to the YourGutPlus website, this is the first scientific trial of their probiotic product, although I understand it was originally being used by the research team at Bedford Hospital for a trial investigating its potential in supporting cancer patients. This hasn’t to my knowledge been published.
I only prescribe probiotics that have been shown to have specific benefits by double-blind, randomised controlled clinical trials. For example, the probiotics I prescribe for Long Covid tend to be ones that have been shown to lower inflammatory markers (such as Lactocaseibacillus rhamnosus GG or improve constipation such as Limosilactobacillus reuteri DSM 17938). Perhaps due to the understandable publicity, YourGutPlus is currently sold out, however I would want stronger evidence of its clinical efficacy to prescribe it to clients in my Microbiome Analysis practice.
Furthermore, many probiotics are unsuitable for people with Long Covid due to histamine issues. I would need each of the YourGutPlus strains thoroughly assessed for histamine production or degradation, before I could be confident this product was safe for the treatment of Long Covid or post-COVID symptoms.
I look forward to future clinical trials for microbiome interventions in Long Covid
The results of this trial show promise, especially with regards to the digestive symptoms in older men, and I hope there might be further trials, that will include a randomised control group and are double-blinded (so that neither researcher nor participant know whether the patient is taking the probiotic or a placebo).
I’m also really pleased to hear the research team has gone on to trial a capsule containing polyphenol-rich food extracts, also sold by YourGutPlus and will look forward to reviewing the results. It’s fantastic to see such interest in microbiome interventions in treating post-Covid symptoms. I am continuing to follow the growing research in this area with interest, and post about exciting developments on my Instagram profile and Facebook page.
REFERENCE
Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Influence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182.
Viola Sampson BSc is a Microbiome Analyst practising in London UK and online. You can book a consultation, or get in touch to find out more.