The purpose of this study is to evaluate the effects of fermented foods on bacterial gutmicrobiome diversity of long-COVID subjects.
This will be a single-center, longitudinal randomized controlled trial assessing a high
fermented food diet intervention among patients with long COVID.
The investigators will adapt the high fermented food diet intervention previously
described by Wastyk et al to our population of patients with long COVID. A list of people
meeting inclusion criteria who are open to research participation will be generated by
the study team members working in the long COVID clinic; eligible patients will be
contacted by a different member of the study team (not working in the long COVID clinic).
Participants who agree to take part in the study will be randomized using REDCap into one
of two arms, a control arm (no diet intervention), or an intervention arm. 20
participants will be assigned to each group (40 total). The study will consist of 2
in-person visits at baseline and week 13. There will be weekly phone calls during weeks 1
through 12 for participants on the intervention arm; participants in the control arm will
be contacted as needed to ensure that they continue to document their diet three days a
week.
All participants will provide a total of two stool samples (baseline and week 13), and
undergo psychometric evaluation with Hospital Anxiety and Depression Scale (HADS) A/D,
Impact of Event Scale - revised (IES-R), Montreal Cognitive Assessment (MoCA)-blind and
European Quality of Life 5 Dimensions 5 Level Version (EuroQol-5D-5L) (baseline and week
13). Demographic information on the subjects will also be collected (age, gender, past
medical history including mental health diagnoses or cognitive diagnoses, time of COVID
infection, etc).
During the baseline visit, the investigators will interview all study participants and
ask participants to provide details about their diet and any use of probiotic foods or
supplements. All participants will install the food tracking application, Mayo Clinic
Diet App, on their personal smart device and will receive instructions on how to use it
by a study team member. An account for each participant will be set up by the study team
and participants will be given a username and password. The investigators will have
access to the data entered. Participants will be instructed to document their food intake
at least three days every week, two weekdays and one weekend day as was done in the study
by Wastyk et al. After the study, participants may change their password if they would
like to continue food tracking.
Intervention Group:
Participants assigned to the intervention arm will receive an in-person teaching session
delivered by a trained team member. The session will include introductory education on
microbiome and a description on a variety of probiotic fermented foods commercially
available (fermented dairy products, fermented vegetables, fermented non-alcoholic
drinks). Participants will be able to choose their own probiotic fermented foods based on
this education and taste preference.
After the visit, intervention arm participants will begin to incorporate probiotic
fermented foods into their diet during weeks 1-4 of the study (ramp up phase).
Participants will start with one serving of fermented food of their choice a day,
increasing to 6+/day as tolerated by the end of week 4. Weeks 5-12 will serve as the
intervention maintenance phase, with the target of a daily intake of 6+ servings per day
of fermented foods.
Fermented food intake will be reported as the average number of servings per day for each
week of the intervention. One serving of probiotic fermented foods will be defined as:
kombucha, yogurt, kefir, buttermilk, kvass, other probiotic fermented liquids = 6 oz,
kimchi, sauerkraut, other probiotic fermented veggies = 1/4 cup, vegetable brine
drink/gut shot from approved list = 2 oz.
Food logs will be reviewed by the investigators to assess compliance and provide
recommendations to increase amounts or variety of fermented foods in the diet as
tolerated. Investigators will interact weekly with participants in the intervention arm
by phone or zoom to review probiotic fermented food intake, answer questions, inquire
about any gastrointestinal symptoms such as bloating or upset stomach, and provide
motivation to continue with the diet. Study participants in the intervention arm will
also be asked to assess their overall compliance with the diet on a scale of 0-10, with
zero being "not at all" and 10 being "exactly as recommended [during the specific phase
of the study]".
Control Group:
The participants in the control arm will only complete the baseline and week 13 visits.
Participants in the control arm will be contacted as needed to ensure that they document
their regular food intake 3 days a week. Control group participants will not be asked to
make any changes to their diet, only to document their regular diet 3 days a week.
At approximately 13 weeks, all participants will collect and return a stool sample and
repeat the study questionnaires. Participants will be able to complete the questionnaires
in person, virtually, or by phone.
Other: Fermented foods
Participants randomized to the intervention arm will begin to incorporate probiotic
fermented foods into their diet during weeks 1-4 of the study (ramp up phase). They will
start with one serving of fermented food of their choice a day, increasing to 6+/day as
tolerated by the end of week 4. Weeks 5-12 will serve as the intervention maintenance
phase, with the target of a daily intake of 6+ servings of fermented foods.
Other: Control
No information on incorporation of fermented foods will be provided for subjects in the
control arm.
Inclusion Criteria:
1. Adult (> 18 years old)
2. Patients who have long COVID symptoms
a. Long COVID will be defined as: i. A previously documented COVID + infection
within the last year ii. A presence of neurological symptoms that started within 4
weeks of the COVID infection (fatigue, difficulty concentrating, depression,
anxiety) as per CDC definition of Long Covid.
3. Own a smart device capable of downloading a food logging application. Able to
understand and document informed consent
4. Seen in the Mayo Clinic long-COVID Clinic within the Department of General Internal
Medicine
Exclusion Criteria:
1. History of dementia, moderate or severe cognitive dysfunction, developmental delay,
psychotic disorders such as schizophrenia
2. Unable to tolerate oral foods
3. Potential contraindications to a fermented food diet (chronically immunosuppressed
including organ transplant recipients)
4. Neutropenic as listed in the "active problems" list in the EMR
5. Undergoing chemotherapy at the time of consent
6. Taking MAOIs at the time of consent.
7. Active uncontrolled inflammatory bowel disease including ulcerative colitis, Crohn's
disease, indeterminate colitis, irritable bowel syndrome (moderate or severe),
infectious gastroenteritis, colitis or gastritis, Clostridium difficile infection
(recurrent), malabsorptive diseases (such as Celiac disease), major surgery of the
GI tract with the exception of cholecystectomy and/or appendectomy in the past 5
years, or any major bowel resection at any time.
8. A reported consumption of 2 servings of probiotic fermented food per day in their
normal baseline diet.
9. Pregnancy
Mayo Clinic
Rochester, Minnesota, United States
Liousmila V Karnatovskaia, MD, Principal Investigator
Mayo Clinic