Table 1.

SPIRIT schedule of enrolment and assessments

#	Timepoint	Week-0 baseline	Week-1 follow-up	Week-6 follow-up	Week-12 follow-up
		T1	T2	T3	T4
1	Enrolment
	Eligibility screening	x
	Informed consent	x
	Allocation	x
2	Assessment
	CRF01 Case Record Forma	x
	CRF02 FW & ADRb	x	x	x	x
	CRF03 ESAS	x		x	x
	CRF04 EQ-5D-5 L	x		x	x
	CRF05 Food Frequency Questionnaire	x		x	x
3	Blood Samples, Serum
	Blood Chemistryc	x			x
	Cytokinesd	x			x
	Bacterial Metabolitese	x			x
	Pharmacokinetics parameters	x		x
	Pharmacogenetics parameters	x		x
4	Feces Samples
	Fecal Microbiome Profile	x			x
	Fecal Bile Acid Profilef	x			x
	Fecal SCFAsg and BCFAsh	x			x
5	Skin Samples
	Skin Microbiome Profile	x			x
6	Saliva Samples
	Oral Microbiome Profile	x			x

^aDemographic and Epidemiological Factors: age, weight, height, waist circumference, hip circumference, neck circumference, alcohol consumption, smoking status, occupation, monthly income, method of health payment, and highest education

^bFollow up and adverse drug reaction: vital signs, physical examination, lab results to assess liver, kidney and heart function, pharmacokinetic record form, drug tolerance assessment form, and adverse event assessment form

^cBlood Chemistry: lipid profile, liver function test (LFT)

^dCytokines: interleukin-17, interferon-gamma, Interleukin-10, tumor growth factor-beta

^eBacterial Metabolites: lipopolysaccharide binding protein, sCD14 levels, equol, cadaverine

^fFecal Bile Acid Profile: chenodeoxycholic acid, deoxycholic acid, lithocholic acid

^gSCFAs: butyric acid, propionic acid, acetic acid

^hBCFAs: iso-butyric acid