Is a more diverse gut microbiome healthier?

What it is

Diversity is a summary number, not a substance. Within-sample (alpha) diversity counts how many different bacterial types a stool sample contains and how evenly they are spread; metagenomic studies use gene richness as a related measure. Consumer reports often print it as a single score. Ecologists point out that the number carries no information about which organisms are there or what they are doing.

What the research says

Low diversity or low gene richness is repeatedly associated with worse metabolic markers in population studies, and one randomised trial raised diversity with fermented foods while inflammatory markers fell. But diversity is strongly confounded by something as mundane as stool consistency, a high-fibre arm of the same trial raised microbial enzyme capacity without raising diversity at all, and a prebiotic trial lowered diversity while increasing organisms usually called beneficial. Mendelian randomisation gives evidence of causality for specific microbial products such as butyrate, not for the diversity score itself.

Evidence grade: Disputed.

What goes wrong

Faecal transplantation intended to restore a microbiome has caused drug-resistant bloodstream infection in two clinical-trial patients, one of whom died. (Source 1)

• Case report, Moderate certainty.
• Size: 2 patients with ESBL-producing E. coli bacteraemia after FMT in two independent trials.
• Who: adults enrolled in two independent FMT clinical trials.
• How long: not stated in the abstract.
• Result: two cases of ESBL-producing Escherichia coli bacteraemia after FMT, both linked to the same stool donor by genomic sequencing; one of the two patients died.
• Funding: not stated.

We describe two patients in whom extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteremia occurred after they had undergone FMT in two independent clinical trials; both cases were linked to the same stool donor by means of genomic sequencing. One of the patients died.

Antibiotics cut diversity sharply and some species do not come back within six months, which is the clearest human demonstration that diversity can be lost involuntarily. (Source 2)

• Cohort study, Low certainty.
• Size: 12 healthy men.
• Who: healthy young adult men given a 4-day cocktail of meropenem, gentamicin and vancomycin.
• How long: 6 months.
• Result: near-baseline composition by 1.5 months but 9 formerly universal species undetectable in most subjects at 180 days.
• Funding: not stated in the abstract.

The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days.

A commentary on the same episode reports that post-transplant samples from a minority of the tested recipients of this donor's capsules grew ESBL-producing organisms, reported as two separate groups rather than a single pooled rate. (Source 3)

• Case series, Low certainty.
• Size: 22 patients received capsules from the donor; 12 trial patients and 7 C. difficile patients were tested.
• Who: recipients of FMT capsules from a single stool donor.
• How long: post-FMT sampling, timing not stated.
• Result: 5 of 12 tested clinical-trial patients and 4 of 7 tested patients treated for recurrent or refractory C. difficile had post-FMT samples growing ESBL-producing organisms; the commentary states these cannot be definitively linked to the donor.
• Funding: not stated.

Limit of this finding: These are two separate groups of patients with two separate test results, not one combined rate. The commentary says the positive cultures cannot be definitively linked to the donor, so they should not be read as proof that the donor infected all of them.

For 12 tested patients in the clinical trials, 5 post-FMT samples grew ESBL-producing organisms, and for 7 tested patients being treated for recurrent or refractory C. difficile, 4 had post-FMT samples that grew ESBL-producing organisms.

What the evidence supports

People with low gut bacterial gene richness had more adiposity, insulin resistance, dyslipidaemia and inflammation than people with high richness. (Source 4)

• Survey study, Low certainty.
• Size: 292 Danish adults (123 non-obese, 169 obese)
• Who: Danish adults in a population sample.
• How long: cross-sectional with follow-up weight data.
• Result: the low-richness group was 23% of the population; obese individuals in that group gained more weight over time.
• Funding: Novo Nordisk Fonden listed among grants.

individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals

Mendelian randomisation supports a causal effect of specific microbial products on metabolic traits, rather than of a diversity score. (Source 5)

• Cohort study, Moderate certainty.
• Size: 952 normoglycaemic individuals plus genome-wide association summary statistics for 17 traits.
• Who: normoglycaemic adults with genotyping, metagenomes and faecal short-chain fatty acid measurements.
• How long: not applicable.
• Result: host-genetic-driven butyrate production associated with improved insulin response (P = 9.8 x 10-5); abnormal propionate production or absorption causally related to increased type 2 diabetes risk (P = 0.004)
• Funding: not stated in the abstract.

These data provide evidence of a causal effect of the gut microbiome on metabolic traits

A 17-week randomised trial found a fermented-food diet increased microbiota diversity and lowered inflammatory markers. (Source 6)

• Randomized trial, Low certainty.
• Size: 18 per arm.
• Who: healthy adults.
• How long: 17 weeks.
• Result: steady increase in microbiota diversity and decrease in inflammatory markers in the fermented-food arm.
• Funding: not stated in the abstract.

the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers

What the evidence does not support

In the same trial, a high-fibre diet changed the microbiome's enzyme capacity without changing diversity, and the primary immune outcome did not move. (Source 6)

• Randomized trial, Low certainty.
• Size: 18 per arm.
• Who: healthy adults.
• How long: 17 weeks.
• Result: community diversity stable; cytokine response score (primary outcome) unchanged; three immunological trajectories corresponded to baseline diversity.
• Funding: not stated in the abstract.

Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity.

Diversity measurements are strongly confounded by stool consistency, a proxy for gut transit time. (Source 7)

• Survey study, Low certainty.
• Size: 53 healthy women.
• Who: healthy women, faecal 16S rDNA profiling.
• How long: cross-sectional.
• Result: stool consistency negatively correlated with species richness and positively associated with the Bacteroidetes:Firmicutes ratio; enterotypes distributed distinctly across Bristol Stool Scale scores.
• Funding: no grants listed in the record.

Stool consistency strongly correlates with all known major microbiome markers. It is negatively correlated with species richness

A prebiotic that raised organisms usually called beneficial lowered diversity and worsened several cardiometabolic markers, so the direction of the diversity score did not track the outcomes. (Source 8)

• Randomized trial, Low certainty.
• Size: 21 supplemented versus 22 controls within 82 completers.
• Who: adults with overweight or obesity on an ad libitum plant-based diet.
• How long: 10 weeks.
• Result: Shannon diversity reduced; LDL:HDL ratio, IL-10, MCP-1 and TNF-alpha significantly elevated in the prebiotic subgroup; no relationship between baseline Prevotella/Bacteroides ratio and weight change (r = -0.07, P = 0.53)
• Funding: EU Horizon 2020 grant 818318; King Saud bin Abdulaziz University for Health Sciences.

Addition of ITF-prebiotics on top this naturally fiber-rich background selectively changes gut microbiota composition and attenuates some of the realized cardiometabolic benefits.

Microbial ecologists argue that a diversity number on its own does not explain community outcomes. (Source 9)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: not applicable (commentary in The ISME Journal by a microbial ecologist)
• How long: not applicable.
• Result: no effect estimate; argues diversity should be a starting point for inquiry rather than an answer.
• Funding: not stated.

the relationships between diversity and emergent properties of a community, such as its stability, productivity or invasibility, are much more nuanced

Where the research disagrees

Whether alpha diversity is a meaningful health indicator

• Le Chatelier and colleagues (Nature, 2013), cross-sectional metagenomics in 292 Danish adults: individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals (Source 4)
• Shade (The ISME Journal, 2017), commentary drawing on traditional and microbial ecology: I argue that diversity without context provides limited insights into the mechanisms underpinning community patterns. (Source 9)

A common belief, and what the research shows

The belief: A higher microbiome diversity score means you are healthier, and raising it should be the goal.

What the research shows: Diversity is associated with health markers but is confounded and not reliably improvable to order. Stool consistency alone shifts it: "It is negatively correlated with species richness". A randomised prebiotic study lowered Shannon diversity while raising Bifidobacterium and Faecalibacterium and worsening several markers, and the causal evidence that exists points at butyrate and propionate production rather than at the diversity number.

Questions and answers

Gut microbiome diversity is a count of how many different bacterial types are in a stool sample and how evenly they are distributed; metagenomic studies use the number of distinct microbial genes as a related measure of richness. It is a summary statistic of a community, not an organism or a nutrient. Ecologists distinguish within-sample (alpha) diversity from differences between samples. (Source 9)

Diversity itself does nothing; the organisms do. What the causal evidence supports is the output of particular microbes: Mendelian randomisation in 952 people linked genetically driven butyrate production to better insulin response and propionate abnormalities to higher type 2 diabetes risk. Diversity scores are best read as a rough proxy for a community with a wide metabolic repertoire. (Source 5)

Higher is associated with better metabolic markers in population studies, but it is not reliably better. A 10-week randomised prebiotic study reduced Shannon diversity while increasing Bifidobacterium and Faecalibacterium, and several inflammatory and lipid markers rose. Diversity also rises with firmer stools and slower transit, so the number partly reflects plumbing rather than health. (Source 8)

The one randomised human trial that moved diversity did so with fermented foods over 17 weeks, in 18 people per arm, alongside a fall in inflammatory markers. The high-fibre arm of the same trial did not raise diversity. This is what the trial did, not a recommendation. (Source 6)

The question mostly runs the other way: nobody sets out to reduce diversity, but antibiotics do it. Four days of meropenem, gentamicin and vancomycin in healthy men partially eradicated the gut community, with some species still missing after 180 days. There is also a measurement quirk to note, since faster transit and looser stools go with lower measured richness. (Source 2)

Antibiotic exposure is the best-documented cause of lost richness in adults, and birth by caesarean, antibiotic prophylaxis in labour and not being breastfed shape an infant's community from the start. Diet matters too, but the trial evidence shows only fermented foods raising diversity within months. Stool consistency and transit time also change the measured number without anything being truly missing. (Source 10)

Fermented foods were the intervention that raised diversity in the randomised trial; plant fibre raised the microbiome's glycan-degrading enzyme capacity without raising diversity. A separate randomised sub-study of 20 g/day chicory-type inulin lowered diversity while raising Bifidobacterium and Faecalibacterium. So food changes the community measurably, but not always in the direction a diversity score rewards. (Source 6)

In a Danish population sample, the 23% of people with low bacterial gene richness had more adiposity, insulin resistance, dyslipidaemia and inflammation, and the obese people among them gained more weight over follow-up. This is an observational association: the authors describe it as identifying people who may be at increased risk, not as a cause of disease. No trial has shown that raising a diversity score by itself changes clinical outcomes. (Source 4)

Diversity is measured by sequencing a stool sample, but the number is sensitive to how the sample was taken and processed. The Microbiome Quality Control project found variability depended most on specimen type and origin, then DNA extraction, handling and bioinformatics, across 15 laboratories and nine pipelines. Stool consistency alone shifts measured richness, so a single consumer diversity score is weak evidence about a person. (Source 11)

Is microbiome diversity causally linked to health, or only associated with it?

Almost all of the evidence linking diversity to health is observational: low gene richness travels with adiposity, insulin resistance and inflammation in population samples, and the authors of the largest such study framed their result as identifying people who may be at increased risk. Where causal methods have been applied, they support specific microbial outputs such as butyrate and propionate rather than the diversity score itself. One randomised trial raised diversity with fermented foods and saw inflammatory markers fall, which is the closest thing to interventional evidence, but it involved 18 people per arm.

Is a higher diversity score always better?

No. A randomised prebiotic sub-study reduced Shannon diversity while increasing Bifidobacterium and Faecalibacterium, and inflammatory and lipid markers rose rather than fell. Measured richness is also negatively correlated with stool consistency, so transit time alone moves the number. A microbial ecologist writing in The ISME Journal argues that diversity without context gives limited insight into what a community is doing.

What are the risks of trying to change diversity deliberately?

Faecal microbiota transplantation, the most aggressive way to change a gut community, transmitted drug-resistant E. coli from a single donor to trial participants; one immunocompromised man died of severe sepsis eight days after his final dose. Antibiotics reliably reduce diversity, and some species had not returned in healthy men six months after a four-day course. Neither is a routine consumer choice, but both show that the community can be moved and that the movement is not always benign.

References

1. New England Journal of Medicine. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. 2019. PMID 31665575, DOI 10.1056/NEJMoa1910437. Read the source
2. Nature Microbiology. Recovery of gut microbiota of healthy adults following antibiotic exposure. 2018. PMID 30349083, DOI 10.1038/s41564-018-0257-9. Read the source
3. Society for Healthcare Epidemiology of America. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant - SHEA commentary summarising DeFilipp et al., New England Journal of Medicine 2019;381:2043-2050. 2019. Read the source
4. Nature. Richness of human gut microbiome correlates with metabolic markers. 2013. PMID 23985870, DOI 10.1038/nature12506. Read the source
5. Nature Genetics. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. 2019. PMID 30778224, DOI 10.1038/s41588-019-0350-x. Read the source
6. Cell (text read from the University of California eScholarship repository copy). Gut-microbiota-targeted diets modulate human immune status. 2021. PMID 34256014, DOI 10.1016/j.cell.2021.06.019. Read the source
7. Gut. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. 2016. PMID 26069274, DOI 10.1136/gutjnl-2015-309618. Read the source
8. Frontiers in Nutrition. Supplementation with inulin-type fructans affects gut microbiota and attenuates some of the cardiometabolic benefits of a plant-based diet in individuals with overweight or obesity. 2023. DOI 10.3389/fnut.2023.1108088. Read the source
9. The ISME Journal. Diversity is the question, not the answer. 2017. PMID 27636395, DOI 10.1038/ismej.2016.118. Read the source
10. Nature. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. 2019. PMID 31534227, DOI 10.1038/s41586-019-1560-1. Read the source
11. Nature Biotechnology. Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium. 2017. PMID 28967885, DOI 10.1038/nbt.3981. Read the source