Gut microbiota changes associated with frailty in older adults: A systematic review of observational studies

Table 1 Main characteristics of the included studies in this review

Ref.	Picca et al[19], 2020	Van Tongeren et al[16], 2005	Xu et al[17], 2021	Lim et al[18], 2021		Zhang et al[22], 2020	Margiotta et al[20], 2020	Ticinesi et al[26], 2017	Haran et al[24], 2018	Haran et al[23], 2021	Larson et al[25], 2020	Zhang et al[21], 2022
Study design	CSS	CSS	CSS	CSS		CSS	CSS	CCS	CHS	CHS	CHS	CSS
Participants	Samples	35	23	94	176	27	64	76	23	166	47	181
	Age (years)	> 70	70-100	80.7 ± 5.7	74.7	81.63 ± 7.90	≥ 65	83.3 ± 7.5	≥ 65	86.2 ± 9.1	> 65	≥ 65
	Male/female	20/15	4/19	44/50	54/122	17/10	43/21	39/37	23	30/136	47	72/109
Genetic analysis	16S rRNA V3-V4	Fluorescence in situ hybri dization	16sRNA V3-V4	16S rRNA		16S rRNA	16sRNA V3-V4	16S rRNA	metagenomic sequencing	metagenomic sequencing	metagenomic sequencing	16sRNA V3-V4
Frailty diagnosis	Short physical performance battery	Groningen Frailty Indicator	Fried's definition	Frailty index		Rockwood Frailty Index	Fried’s Frailty Phenotype	Rockwood Index	CFS	CFS	Rockwood Index	Frailty Phenotype
Outcome measurement	α-diversity, β-diversity, family level, genus level	Genus level, species level	α-diversity, β-diversity, phylum level, genus level	α-diversity, genus level, dpecies level		α-diversity, β-diversity, phylum level, family level, genus level	α-diversity, phylum level, genus level	α-diversity, β-diversity	β-diversity, species level	α-diversity, β-diversity, species level	Genus level, species level	β-diversity, phylum level, genus level

CSS: Cross-sectional study: CCS: Case-control study; CHS: Cohort study; CFS: Clinical Frailty Scale.

Table 2 The Agency for Healthcare Research and Quality assessment for the cross-sectional study

Ref.	Item 1	Item 2	Item 3	Item 4	Item 5	Item 6	Item 7	Item 8	Item 9	Item 10	Item 11	Scores
Picca et al[19], 2020	Yes	Yes		Yes	Yes			Yes		Yes		6
Van Tongeren et al[16], 2005	Yes	Yes		Yes	Yes		Yes			Yes		6
Xu et al[17], 2021	Yes			Yes	Yes		Yes	Yes		Yes		6
Lim et al[18], 2021	Yes	Yes			Yes		Yes	Yes		Yes		6
Zhang et al[22], 2020	Yes	Yes		Yes	Yes	Yes	Yes	Yes		Yes		8
Margiotta et al[20], 2020	Yes	Yes		Yes	Yes		Yes	Yes		Yes		7
Zhang et al[21], 2022	Yes	Yes	Yes		Yes	Yes	Yes	Yes				7

Yes is one point, the total number of stars represents a number of points. Item 1: Define the source of information (survey, record review)? Item 2: Inclusion and exclusion criteria for exposed and unexposed subjects (cases and controls) or refer to previous publications? Item 3: Indicate time period used for identifying patients? Item 4: Indicate whether or not subjects were consecutive if not population-based? Item 5: Indicate if evaluators of subjective components of study were masked to other aspects of the status of the participant? Item 6: Describe any assessments undertaken for quality assurance purposes (e.g., testretest of primary out come measuroments)? Item 7: Explain any patient exclusions from analysis? Item 8: Describe how confounding was assessed and/or controlled? Item 9: If applicable, explain how missing data were handled in the analysis? Item 10: Summarize patient response rates and completeness of data collection? Item 11: Clarify what follow-up, if any, was expected and the percentage of patients for which incomplete data or follow-up was obtained?

Table 3 The Newcastle-Ottawa Scale assessment for the cohort studies

Ref.	Selection				Comparability		Exposure			Scores
	Representativeness of selection of the non- exposed cohort	Selection of the non-exposed cohort	Ascertainment of exposure	Demonstration that outcome of interest was not present at start of study	Comparability of cohort on the basis of the design or analysis	Ascertainment of outcome	Ascertainment of outcome	Was follow-up long enough for outcomes to occur	Adequacy of follow-up of cohorts
Haran et al[24], 2018	Yes	Yes			Yes	Yes, Yes				5
Haran et al[23], 2021	Yes	Yes				Yes, Yes		Yes	Yes	6
Larson et al[25], 2020	Yes	Yes			Yes	Yes, Yes				5

Yes is one point, the total number of stars represents a number of points.

Table 4 The Newcastle-Ottawa Scale assessment for the case-control study

Ref.	Selection				Comparability	Exposure			Scores
	Adequate definition of case	Representativeness of the case	Selection of controls	Definition of controls	Control for important factor	Ascertainment of exposure	Same method of ascertain for cases and controls	Non-responsese rate
Ticinesi et al[26], 2017	Yes	Yes	Yes	Yes	Yes	Yes, Yes		Yes	7

Yes is one point, the total number of stars represents a number of points.