7.7 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 this sample is pretty similar in overall diversity to the healthy samples in our database.

##          Shannon
## 906356  1.821589
## 1168330 1.932456
## [1] 1.92671
The blue line is CT.

Figure 7.8: The blue line is CT.

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

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

First let’s make a similarity plot it to see if we can spot something unusual:

Nothing special there. She seems firmly in the middle of most of the rest of the people.

Now let’s look for specific microbes at the phylum level:

2018-05-09 2017-06-30 2017-07-25
Firmicutes 43.79 79.46 57.10
Bacteroidetes 41.20 13.73 20.24
Actinobacteria 8.68 3.94 13.28
Verrucomicrobia 4.87 1.03 0.00
Proteobacteria 1.10 1.35 9.39
Synergistetes 0.20 0.00 0.00
Lentisphaerae 0.13 0.05 0.00
Acidobacteria 0.01 0.00 0.00
Candidatus Saccharibacteria 0.01 0.00 0.00
Euryarchaeota 0.00 0.56 0.00
Fibrobacteres 0.00 0.44 0.00

Nothing obviously different there than with others I’ve seen. Might be nice to see more Verrucomicrobia in the second (7-25) sample, but nothing pops as particularly special. How about the genus level:

2018-05-09 2017-06-30 2017-07-25
Bacteroides 36.18 3.86 15.47
Lachnospira 10.01 0.57 0.17
Collinsella 7.15 2.84 8.18
Blautia 6.24 8.12 17.41
Fusicatenibacter 6.16 3.91 2.90
Akkermansia 4.87 1.03 0.00
Pseudobutyrivibrio 3.84 4.97 3.26
Streptococcus 2.89 0.08 2.05
Dialister 2.45 0.00 0.75
Sarcina 2.34 2.54 0.18
Anaerostipes 2.27 3.98 0.88
Roseburia 1.27 17.50 7.38
Alistipes 1.24 2.46 1.55
Bifidobacterium 1.19 0.72 4.86
Clostridium 1.07 2.24 0.30
Dorea 1.01 2.34 0.08
Parabacteroides 0.95 0.75 2.05
Faecalibacterium 0.25 4.49 8.05
Subdoligranulum 0.18 1.51 4.46
Parasutterella 0.10 0.01 2.68
Intestinibacter 0.09 1.73 0.69
Megasphaera 0.07 0.00 4.89
Phascolarctobacterium 0.00 1.23 0.77
Thalassospira 0.00 0.00 5.30
Butyrivibrio 0.00 8.42 0.00

The most striking finding is how different the second sample is from the first. Why?

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. Which microbe disappeared in the second sample?

##                         664303                tax_name
## Dialister                24483               Dialister
## Clostridioides            8112          Clostridioides
## Eggerthella               2644             Eggerthella
## Cloacibacillus            1983          Cloacibacillus
## Eisenbergiella            1479          Eisenbergiella
## Paraprevotella            1288          Paraprevotella
## Coprobacter                918             Coprobacter
## Megasphaera                717             Megasphaera
## Dielma                     313                  Dielma
## Prevotella                 201              Prevotella
## Candidatus Stoquefichus    201 Candidatus Stoquefichus
## Corynebacterium             89         Corynebacterium
## Romboutsia                  78              Romboutsia
## Campylobacter               56           Campylobacter
## Solobacterium               56           Solobacterium
## Atopobium                   44               Atopobium
## Mobiluncus                  44              Mobiluncus
## Anaerococcus                33            Anaerococcus
## Pseudoflavonifractor        22    Pseudoflavonifractor
## Porphyromonas               22           Porphyromonas
## Enterobacter                 0            Enterobacter
## Finegoldia                   0              Finegoldia
## Peptoniphilus                0           Peptoniphilus
## Thalassospira                0           Thalassospira
## Gordonibacter                0           Gordonibacter
## Succiniclasticum             0        Succiniclasticum

and vice versa:

% Unique to first sample
Butyrivibrio 8.42
Methanobrevibacter 0.56
Fibrobacter 0.44
Marvinbryantia 0.31
Asaccharospora 0.20
Howardella 0.09
Peptococcus 0.05
Anaerosporobacter 0.03
Delftia 0.02
Acetitomaculum 0.01
Enterorhabdus 0.01
Sporobacter 0.01
Pasteurella 0.01

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

##                 2017-05-21 2017-05-21
## Firmicutes         55.5455    48.8869
## Bacteroidetes      28.4884    41.6446
## Proteobacteria      8.7142     2.5150
## Actinobacteria      6.9858     6.8600
## Verrucomicrobia     0.2245     0.0691
## Lentisphaerae       0.0265     0.0242
## Fibrobacteres       0.0147     0.0000
##                        2017-05-21 2017-05-21
## Bacteroides               22.3166    34.4732
## Faecalibacterium          15.3337     1.3630
## Blautia                    9.6035    12.2878
## Roseburia                  6.6342    11.5717
## Sutterella                 4.3859     0.1504
## Bifidobacterium            4.2248     3.2795
## Thalassospira              4.1717     2.3195
## Subdoligranulum            3.6738     1.4650
## Fusicatenibacter           2.7225     2.7554
## Pseudobutyrivibrio         2.6708     2.6257
## Collinsella                2.4773     3.3089
## Anaerostipes               1.7357     3.7396
## Parabacteroides            1.4846     3.3885
## Clostridium                1.4388     1.1312
## Lachnospira                1.3989     1.1796
## Alistipes                  1.2866     1.5826
## Sarcina                    1.2630     1.1762
## Erysipelatoclostridium     1.0813     1.3958
## Dorea                      1.0030     1.4304
## Intestinibacter            0.8036     0.3286
## Anaerotruncus              0.5347     0.6711
## Butyricimonas              0.4091     0.2836
## Dialister                  0.3678     0.5535
## Streptococcus              0.2511     0.3666
## Odoribacter                0.2038     0.2992

7.7.1 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.

7.7.2 SJ

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

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

##              taxa   max min median        mean          sd original
## 1       Dialister 14270   0   3287  3462.26578  2462.66874    36001
## 2     Collinsella 50105 163  12294 12571.26578  7155.75010    55137
## 3 Subdoligranulum 50996 340  18932 18691.26578 11035.85217    66619
## 4     Allisonella   374   0     25    50.62126    71.51501     1143

and species:

##                                          taxa   max min median
## 1                Faecalibacterium prausnitzii 29259   0  392.5
## 2                       Dorea formicigenerans  2545   0   44.0
## 3             Pseudoflavonifractor capillosus    37   0    0.0
## 4                      Roseburia intestinalis  1317   0    0.0
## 5                         Dialister sp. E2_20    91   0    0.0
## 6                    Bacteroides massiliensis  9801   0    0.0
## 7                   Subdoligranulum variabile  2985   0   35.5
## 8                        Alistipes finegoldii  1306   0    0.0
## 9                   Anaerosporobacter mobilis    32   0    0.0
## 10                     Bacteroides salyersiae  2094   0   98.5
## 11                           Blautia wexlerae  6654   0    0.0
## 12                    Bacteroides sp. EBA5-17  2168   0    0.0
## 13                        Anaerostipes hadrus   727   0    0.0
## 14                 Anaerostipes sp. 5_1_63FAA  3173   0    0.0
## 15            Fusicatenibacter saccharivorans  3614   0    0.0
## 16 Faecalibacterium sp. canine oral taxon 147 10188   0    0.0
## 17                       Bacteroides vulgatus 29768   0  302.5
## 18                   Odoribacter splanchnicus  1644   0   24.5
## 19                     Parabacteroides merdae  1525   0  125.0
## 20                    Collinsella aerofaciens 11224   0    0.0
## 21                          Dorea longicatena  2334   0    0.0
## 22                       Bacteroides sp. AR20  2537   0    0.0
## 23                    Akkermansia muciniphila  1391   0    0.0
## 24                     Bacteroides sp. 35AE37  4477   0    0.0
## 25                Adlercreutzia equolifaciens   458   0   19.0
## 26           Parasutterella excrementihominis  2001   0   52.0
## 27                     Alistipes indistinctus    79   0    2.0
## 28                             Blautia faecis  3532   0  171.5
## 29                   Bacteroides intestinalis    52   0    0.0
## 30                       Alistipes putredinis  3773   0    0.0
## 31               Allisonella histaminiformans    22   0    0.0
## 32                Parabacteroides goldsteinii   213   0    0.0
## 33                  Blautia hydrogenotrophica   144   0    0.0
## 34                         Bacteroides clarus  1076   0    0.0
## 35                          Blautia stercoris   361   0    8.0
## 36                           Prevotella bivia    37   0    0.0
## 37                           Blautia producta    10   0    0.0
## 38                     Alistipes massiliensis    62   0    0.0
## 39                        Barnesiella sp. 177   282   0    0.0
##             mean           sd original
## 1  3752.11204013 4882.5503742    69471
## 2    91.48160535  145.9856427     3400
## 3     2.32775920    4.2662163      381
## 4    19.30769231   80.7402662     1616
## 5     0.33612040    3.9590534    35559
## 6   221.79598662  806.8387379    40667
## 7   357.79096990  529.7754761    24687
## 8    34.71237458  129.1359154    14699
## 9     0.33612040    2.3091979       91
## 10  211.80100334  287.9392248    11253
## 11  197.24916388  536.8222241    11268
## 12    6.48160535   91.2366674     2241
## 13    2.59030100   33.1286165      762
## 14  262.70401338  450.1535056    18160
## 15  212.78260870  389.9180856    11024
## 16  281.21906355 1110.5934266    41993
## 17 1360.66889632 2237.7081870   121513
## 18   59.05852843   99.2529293     8539
## 19  231.08193980  283.1613085    47010
## 20   39.70401338  520.7003443    45607
## 21   68.08026756  146.5396062    10734
## 22  212.99163880  442.7979014    17459
## 23    5.29431438   62.5869740     8203
## 24   95.68896321  431.2631095     6206
## 25   46.35618729   66.6119180     3735
## 26  241.55852843  322.1125136    22323
## 27    8.09197324   11.2709839     1906
## 28  359.41471572  470.1923003     4315
## 29    0.77926421    4.1779638       60
## 30   14.49665552  172.7936943     9591
## 31    0.61705686    2.0946234     1143
## 32    0.86120401   11.1024979     2637
## 33    0.24414716    5.8890289      198
## 34    1.95819398   44.0826837     8218
## 35   24.88127090   37.0682871     9042
## 36    0.15217391    1.8133842      365
## 37    0.01672241    0.4089304       30
## 38    0.16889632    2.7209533      594
## 39   11.59698997   28.2463402     1814

7.7.3 Mr. C

7.7.4 FF

Here’s a person from Norway who has long suffered from IBS.

7.7.5 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.