7.8 Gut Issues

NOTE: THIS CHAPTER IS AN EARLY DRAFT

Probably the most common reason people are motivated to study their microbiome is gut dysbiosis. The word “dysbiosis” is as good a diagnosis as any for a problem that is often frustratingly difficult to pin down.

Ten years ago, CT was in excellent health, active in sports with a lean, muscular build. But after a trip to China, and a bout of what he thought was food poisoning, he hasn’t been the same. Food allergies, sensitivities to chemicals and bright lights, fatigue, and unexplained muscular problems. Doctors were baffled. Nothing seemed to help, and it looked like he might simply have to accept that this was the new way he’d have to live.

The first thing to note is that CT’s samples are pretty similar in overall diversity to the healthy samples in our database. (Figure 7.10)

The blue lines are CT's samples.

Figure 7.10: The blue lines are CT’s samples.

So what might be driving CT’s issues?

Let’s look at the microbes that are significantly different in CT than in our database of healthy people. The genus-level microbes listed in Figure ?? are outliers.

Table 7.1: Mr. C Outliers
taxa max min median mean sd original
Haemophilus 0.396 0 0 0.030 0.072 1.739
Parvibacter 0.037 0 0 0.003 0.007 0.039

From this it appears CT has far higher Haemophilus than the healthy people. What might that mean?

Can we find other people with similar high levels? Here’s a look at the top 10 most abundant samples in our database. Note that all are unhealthy.

Condition Abundance
Dysbiosis 6.0841
Dysbiosis 3.3989
Dysbiosis 1.7394
Cancer 1.2119
Dysbiosis 1.1825
Dysbiosis 1.1379
NA 0.8869
Dysbiosis 0.6256
NA 0.6032
Cancer 0.5932

7.8.1 CB

CB is a health-conscious woman who has long suffered from gut issues.

Let’s start with a heatmap of all her gut samples to see if we can spot any patterns

Table 7.2: CB Outliers
taxa max min median mean sd original
Clostridium 2.770 0 0.644 0.828 0.564 4.462
Lachnospira 7.017 0 0.553 1.076 1.313 10.101
Eggerthella 0.269 0 0.006 0.028 0.050 0.841
Dielma 0.102 0 0.000 0.005 0.013 0.330
Syntrophococcus 0.038 0 0.000 0.001 0.006 0.050
Acetanaerobacterium 0.005 0 0.000 0.000 0.001 0.023
Curvibacter 0.000 0 0.000 0.000 0.000 0.023

7.8.2 NJ1

Hard to tell from this single case. How about if we look at another person (“NJ1”)

Here are all the outliers in NJ1’s samples:

## [1] "before ACHIM"
## 
## 
## Table: (\#tab:caseStudyGutNJ1Outliers)NJ1 Outliers 664303
## 
## taxa               max     min   median    mean      sd   original
## --------------  ------  ------  -------  ------  ------  ---------
## Lachnospira      7.017   0.000    0.553   1.076   1.313     10.010
## Holdemania       0.070   0.000    0.006   0.008   0.011      0.121
## Collinsella      6.515   0.006    1.321   1.751   1.333      7.146
## Catabacter       0.012   0.000    0.000   0.001   0.002      0.014
## Acetatifactor    0.000   0.000    0.000   0.000   0.000      0.002
## 
## [1] "High amonia"
## 
## 
## Table: (\#tab:caseStudyGutNJ1Outliers)NJ1 Outliers 153887
## 
## taxa               max   min   median    mean      sd   original
## --------------  ------  ----  -------  ------  ------  ---------
## Butyrivibrio     6.165     0    0.000   0.216   0.793      8.424
## Fibrobacter      0.072     0    0.000   0.005   0.015      0.437
## Oscillibacter    0.499     0    0.017   0.078   0.120      0.666
## 
## [1] "porphyria"
## 
## 
## Table: (\#tab:caseStudyGutNJ1Outliers)NJ1 Outliers 174763
## 
## taxa             max     min   median    mean      sd   original
## ------------  ------  ------  -------  ------  ------  ---------
## Collinsella    6.515   0.006    1.321   1.751   1.333      8.178
## Megasphaera    2.235   0.000    0.001   0.106   0.354      4.894

When I look closer, it appears that much of the difference is driven by one genus, Colinsella, of which she has among the highest abundances I’ve seen. In my own gut samples, I’ve never had more than 5% of that genus, but she has more than 8%. Is that good or bad? Who knows? But it’s something I would spend more time studying.

Clearly different at nearly all taxa. Here are the microbes that went extinct in the second sample:

## Acetanaerobacterium, Acetatifactor, Anaerococcus, Atopobium, Campylobacter, Candidatus Stoquefichus, Christensenella, Cloacibacillus, Clostridioides, Coprobacter, Corynebacterium, Dialister, Dielma, Eggerthella, Eisenbergiella, Enterobacter, Fastidiosipila, Finegoldia, Fusobacterium, Gordonibacter, Megasphaera, Mobiluncus, Paraprevotella, Parvimonas, Peptoniphilus, Porphyromonas, Prevotella, Pseudoflavonifractor, Romboutsia, Solobacterium, Staphylococcus, Succiniclasticum, Thalassospira, Varibaculum

and vice versa:

## Acetitomaculum, Anaerosporobacter, Asaccharospora, Butyrivibrio, Delftia, 
## Enterorhabdus, Fibrobacter, Howardella, Marvinbryantia, 
## Methanobrevibacter, Pasteurella, Peptococcus, Sporobacter

7.8.3 Ed

Let’s look at another case: “Ed” is a German man on a mostly vegetarian diet.

Table 7.3: Ed Outliers
taxa max min median mean sd original

7.8.4 Celiac Patients

L and her friend S suffer from the gluten disorder called Celiac disease.

##                 2017-08-08 2017-06-26
## Firmicutes         53.3713    45.5525
## Bacteroidetes      31.9602    51.0501
## Verrucomicrobia     4.7563     0.1230
## Proteobacteria      4.5754     1.7504
## Actinobacteria      2.7873     1.4615
## Fusobacteria        2.5491     0.0025
##                    2017-08-08 2017-06-26
## Bacteroides           27.7946    38.0893
## Blautia               27.3715     6.1286
## Akkermansia            4.7563     0.1230
## Klebsiella             4.5355     0.0466
## Moryella               3.1931     0.1995
## Roseburia              2.9123     6.4227
## Pseudobutyrivibrio     2.7101     2.4747
## Parabacteroides        2.6289     2.3931
## Faecalibacterium       1.3490    11.4020
## Barnesiella            0.0000     6.0560

I don’t often see L’s level of Fusobacterium. A quick check, though, shows that she’s not the highest.

7.8.5 SJ

His doctor says he has high Klebsiella, but how high is high?

Here are the genus-level microbes that are out of range:

Table 7.4: SJ Outliers
taxa max min median mean sd original
Adlercreutzia 0.371 0 0.031 0.07 0.088 0.374

and species:

Table 7.5: Ed Outliers
taxa max min median mean sd original
Dialister sp. E2_20 0.650 0 0.000 0.016 0.094 3.556
Adlercreutzia equolifaciens 0.371 0 0.031 0.068 0.084 0.374
Bacteroides clarus 0.426 0 0.000 0.019 0.068 0.822
Propionibacterium acnes 0.000 0 0.000 0.000 0.000 0.008
Barnesiella sp. 177 0.050 0 0.000 0.001 0.007 0.181

7.8.6 U5

Another user was recently diagnosed as pre-diabetic and began taking Metformin.

His microbial abundance seems to be in range of healthy people at both genus and species levels.

Interestingly, he had tried a few experiments before going on Metformin: eating an apple daily with yogurt, followed by daily yogurt alone. Here are the results:

7.8.7 Mr. C

Here’s another person. Let’s see which parts of their sample are outliers compared to healthy people.

Table 7.6: Mr. C Outliers
taxa max min median mean sd original
Oscillospira 0.660 0 0.025 0.063 0.119 0.906
Shuttleworthia 0.096 0 0.000 0.007 0.017 0.430

7.8.8 FF

Here’s a person from Norway who has long suffered from IBS. Let’s look at outliers:

Table 7.7: Mr. FF Outliers
taxa max min median mean sd original
Haemophilus 0.396 0 0 0.030 0.072 1.183
Actinobacillus 0.045 0 0 0.001 0.006 0.100
Aggregatibacter 0.029 0 0 0.001 0.004 0.030
Leptotrichia 0.008 0 0 0.000 0.001 0.011

7.8.9 High Proteobacteria

Usually I associate the phylum Proteobacteria with trouble. So when recently somebody showed me results with nearly 10%, I immediately wanted to know more.

db1 %
Bacteroides 22.0727
Blautia 11.0547
Faecalibacterium 10.4940
Parasutterella 7.0378
Alistipes 5.7292
Subdoligranulum 5.3179
Roseburia 3.2436
Pseudobutyrivibrio 2.6146
Lachnospira 2.1729
Barnesiella 2.0692
Desulfovibrio 1.5667
Sarcina 1.4895
Phascolarctobacterium 1.4516
Butyricimonas 1.2098
Parabacteroides 1.1428
Collinsella 1.1149
Anaerostipes 1.0111
Fusicatenibacter 0.8251
Dorea 0.7935
Kluyvera 0.7099
Clostridium 0.4049
Bilophila 0.3986
Flavobacterium 0.3189
Terrisporobacter 0.3125
Odoribacter 0.2771

Most of the Proteobacteria is from the genus Parasutterella. I’m not sure what this one does, but the levels in this sample are much higher than anything I’ve seen before.