Probiotics to treat long covid?

I know, I know, but this is a double-blind study with around 400 hundred subjects published in The Lancet. It’s a little more technical than I like to get with these science-feed posts, but the gist of it is that a treatment that boosts the presence of certain elements in patients’ gut biome succeeded in alleviating several of the worst effects of long covid:

Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms.
In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with, NCT04950803.
Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520–3·397, p=0·0001), memory loss (1·967, 1·271–3·044, p=0·0024), difficulty in concentration (2·644, 1·687–4·143, p<0·0001), gastrointestinal upset (1·995, 1·304–3·051, p=0·0014), and general unwellness (2·360, 1·428–3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036).
Treatment with SIM01 alleviates multiple symptoms of PACS.

The relative abundance of several bacteria from the Bifidobacterium genus (B bifidum, B adolescentis, B longum, Bifidobacterium pseudocatenulatum) as well as Roseburia intestinalis, Roseburia hominis, Faecalibacterium prausnitzii, and Akkermansia muciniphila were significantly increased whereas Ruminococcus gnavus and some from the Klebsiella genus were significantly decreased in the faecal samples at 6 months after SIM01 treatment (false discovery rate <0·05). These changes were not found in the placebo group

Correlation of microbial changes and response to a specific symptom showed that alleviation in different symptoms was associated with distinct changes in the microbiome at both the compositional and functional levels (FDR<0·05; appendix 2 p 11). For instance, Bifidobacterium adolescentis showed positive correlations with alleviation in fatigue, gastrointestinal upset, and memory loss. We also found that alleviation in fatigue and general unwellness correlated with an elevated relative abundance of Bifidobacterium bifidum, whereas alleviation in difficulty in concentration correlated with a positive shift in Bifidobacterium longum.

This double-blind, randomised controlled trial showed that treatment with SIM01 was effective in alleviating multiple symptoms of PACS. We found that SIM01 led to improved gut microbiota composition by promoting the abundance of beneficial bacteria and suppressing that of pathogenic bacteria associated with PACS, such as those of the Klebsiella genus. Microbiome pathway analysis showed that SIM01 was associated with a decrease in the relative abundance of the microbial species involved in the enhancement of urea cycle pathway, which is also known to be associated with PACS. Besides, gut microbiota composition has been linked to host immune response and blood cytokine profiling. Overall, our findings on gut microbiota provided plausible mechanisms to account for the observed clinical benefits of SIM01 in patients with PACS.