Henry Butt

Henry Butt, MSc, PhD, is the Director of Bioscreen (a laboratory specializing in fecal microbial analysis) and a researcher in Newcastle, Australia.

Books

• 2014, Chapter Five in Advances in Clinical Chemistry, Vol. 66, published by Elsevier; "Metabolism in Chronic Fatigue Syndrome," by Christopher W. Armstrong, Neil R. McGregor, Henry L. Butt, and Paul R. Gooley

Notable studies

• 2017 - Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and d-lactic acidosis: a systematic review

  Abstract - Background: The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of d-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of d-lactic acidosis (d-la). Methods: d-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurological symptoms and high d-lactate levels. Fifty-nine d-la episodes were included in the qualitative synthesis comparing d-la symptoms with ME/CFS diagnostic criteria. A narrative review of d-la mechanisms and relevance for ME/CFS was provided. Results: The majority of neurological disturbances reported in d-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported d-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis, although only preliminary evidence supported the role of lactate-producing bacteria in ME/CFS. Limitations: Interpretation of results are constrained by both the breadth of symptoms included in ME/CFS diagnostic criteria and the conservative methodology used for d-la symptom classification. Several pathophysiological mechanisms in ME/CFS were not examined. Conclusions: Shared symptomatology and underlying microbiota–gut–brain interactions raise the possibility of a continuum of acute (d-la) versus chronic (ME/CFS) presentations related to d-lactate absorption. Measurement of d-lactate in ME/CFS is needed to effectively evaluate whether subclinical d-lactate levels affect neurological symptoms in this clinical population.

• 2017, The association of fecal microbiota and fecal, blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome

  "Abstract - Introduction: The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota. Objectives: Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites. Methods: A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput ¹H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9 ± 1.8 SE years old) and twenty-five non-ME/CFS female (33.0 ± 1.6 SE years old). Results: The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA. In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients. Conclusion: Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism

• 2016, Widespread pain and altered renal function in ME/CFS patients

  Abstract - "Background: Widespread pain is noted in many patients with chronic fatigue syndrome (ME/CFS), fibromyalgia and temporomandibular disorders. These conditions usually start as a localized condition and spread to a widespread pain condition with increasing illness duration. Purpose: To aim was to assess the changes in biochemistry associated with pain expression and alterations in renal function. Methods: Forty-seven ME/CFS patients and age/sex-matched controls had a clinical examination, completed questionnaires, standard serum biochemistry, glucose tolerance tests and serum and urine metabolomes in an observational study. Results: Increases in pain distribution were associated with reductions in serum essential amino acids, urea, serum sodium and increases in serum glucose and the 24-hour urine volume; however the biochemistry was different for each pain area. Regression modelling revealed potential acetylation and methylation defects in the pain subjects. Conclusions: These findings confirm and extend our earlier findings. These changes appear consistent with repeated minor inflammatory-mediated alterations in kidney function resulting in essential amino acid deprivation and inhibition of protein synthesis and genetic translation within tissues."

• 2016 - Support for the Microgenderome: Associations in a Human Clinical Population

  "Abstract - The ‘microgenderome’ provides a paradigm shift that highlights the role of sex differences in the host-microbiota interaction relevant for autoimmune and neuro-immune conditions. Analysis of cross-sectional self-report and faecal microbial data from 274 patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) suggests that commensal gut microorganisms may play both protective and deleterious roles in symptom expression. Results revealed significant sex-specific interactions between Firmicutes (Clostridium, Streptococcus, Lactobacillus and Enterococcus) and ME/CFS symptoms (including neurological, immune and mood symptoms), regardless of compositional similarity in microbial levels across the sexes. Extending animal studies, we provide support for the microgenderome in a human clinical population. Applied and mechanistic research needs to consider sex-interactions when examining the composition and function of human microbiota."

• 2015, Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study (Jackson ML, Henry Butt, Ball M, Lewis DP, Bruck D)
• 2015, Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients

  "Abstract - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term multisystem disorder with a central and inexplicably persistent fatigue symptom that is unable to be relieved by rest. Energy metabolism and oxidative stress have been recent focal points of ME/CFS research and in this study we were able to elucidate metabolic pathways that were indicative of their dysfunction. Blood and urine samples were collected from 34 females with ME/CFS (34.9 ± 1.8 SE years old) and 25 non-ME/CFS female participants (33.0 ± 1.6 SE years old). All samples underwent metabolic profiling via 1D 1H Nuclear magnetic resonance spectroscopy and quantitated metabolites were assessed for significance. Blood glucose was elevated while blood lactate, urine pyruvate, and urine alanine were reduced indicating an inhibition of glycolysis that may potentially reduce the provision of adequate acetyl-CoA for the citric acid cycle. We propose that amino acids are being increasingly used to provide an adequate carbohydrate source for the citric acid cycle. We suggest that this is via glutamate forming 2-oxoglutarate through an enzyme that deaminates it and subsequently elevates blood aspartate. Dysfunctional energy metabolism appears to have impacted creatinine and its elevation in urine suggests that it may be used as an alternative for anaerobic ATP production within muscle. A decrease in blood hypoxanthine and an increase in urine allantoin further suggest the elevation of reactive oxygen species in ME/CFS patients. These findings bring new information to the research of energy metabolism, chronic immune activation and oxidative stress issues within ME/CFS."

• 2012, NMR metabolic profiling of serum identifies amino acid disturbances in chronic fatigue syndrome

  "Abstract - Chronic fatigue syndrome (CFS) is a debilitating multisystem disorder characterised by long-term fatigue with a variety of other symptoms including cognitive dysfunction, unrefreshing sleep, muscle pain, and post-exertional malaise. It is a poorly understood condition that occurs in ~ 5 in every 1000 individuals. We present here a preliminary study on the analysis of blood samples from 11 CFS and 10 control subjects through NMR metabolic profiling. Identified metabolites that were found to be significantly altered between the groups were subjected to correlation analysis to potentially elucidate disturbed metabolic pathways. Our results showed a significant reduction of glutamine (P = 0.002) and ornithine (P < 0.05) in the blood of the CFS samples. Correlation analysis of glutamine and ornithine with other metabolites in the CFS sera showed relationships with glucogenic amino acids and metabolites that participate in the urea cycle. This indicates a possible disturbance to amino acid and nitrogen metabolism. It would be beneficial to identify any potential biomarkers of CFS for accurate diagnosis of the disorder."

• 2009, Increased D-Lactic Acid Intestinal Bacteria in Patients with Chronic Fatigue Syndrome
• 2000, Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome
• 2000, Erythrocyte Morphology in Rheumatoid Arthritis and Chronic Fatigue Syndrome: A Preliminary Study

  Abstract - "Erythrocyte deformability and erythrocyte membrane stability are dependent on the erythrocyte cytoskeleton and its relationship with the contents of the cell. Certain internal occurrences such as oxidation of sulphydryl groups on the membrane cytoskeleton or the haemoglobin molecule could alter this relationship and as a consequence, alter the membrane properties and the shape of the cell. It is thus conceivable that in conditions where there is a potential increase in the generation of free radicals, erythrocyte shape could be altered. We investigated the possibility that predictable shape changes occur in erythrocytes from patients with rheumatoid arthritis (RA), a condition associated with free radical damage. We also investigated this possibility in patients with chronic fatigue syndrome (CFS) and whether any such change could be correlated with those seen in RA. Patients with CFS could be divided into two groups based on their erythrocyte morphology. Patients in one of these groups had increased numbers of stomatocytes. Patients with RA had increased numbers of leptocytes."

• 2000, Investigation of Erythrocyte Oxidative Damage in Rheumatoid Arthritis and Chronic Fatigue Syndrome

  Abstract - "A role of free radical scavenging for erythrocytes has previously been demonstrated, which is additional to their established role of gas exchange. In carrying out this role, erythrocytes become damaged by oxidation, which consumes endogenous reducing substances. It was therefore proposed that there exists a link between erythrocyte metabolism (particularly redox metabolism) and erythro-cyte shape and that both of these should be related to erythrocyte deformability. To look for evidence of oxidative damage in vivo, the erythrocytes were assessed for reduced glutathione (GSH), malondial-dehyde (MDA), methaemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) in patients suffering from rheumatoid arthritis (RA), chronic fatigue syndrome (CFS) and healthy control subjects. Full blood counts, serum vitamin B12, erythrocyte folate, serum ferritin, serum iron, serum iron binding capacity and erythrocyte magnesium were also performed on all samples. Patients with RA had increased 2,3-DPG, GSH and metHb when compared with the control group as well as the expected decreased haemoglobin, haematocrit, and serum iron. There was evidence of oxidative damage in CFS with 2,3-DPG metHb and MDA increased in this group. An increase in GSH could also be demonstrated in a sub-group of the CFS patients. This damage may explain the shape changes (presumably accompanied by increased rigidity) that have been reported in erythrocytes in patients suffering from CFS and suggests a role for free radicals in the pathogenesis of CFS."

• 1998, Immunological and Haematological Parameters in Patients with Chronic Fatigue Syndrome

  Abstract - "Red and white blood cell parameter profiles and poke-weed mitogen responses were investigated in 57 CDC-dcfined CFS patients and 34 age-and sex-matched controls. CFS patients had significantly different red and white blood cell profiles compared with controls. Red cell distribution width (RDW) was the primary regression factor differentiating the groups. RDW was positively associated with mean platelet volume (MPV) in control subjects, but negatively correlated with MPV in CFS patients, indicating a reversal of the functional relationship between these parameters in CFS patients. Hematological parameters, and not the immunological parameters studied, were more important in differentiating CFS patients from healthy control subjects. Female CFS patients had significant increases in RDW and mean platelet volume, and decreases in the numbers of T-helper cells, T-cells and lymphocytes compared with control females. These alterations were not observed in corresponding mate comparisons. There were no differences in the pokeweed mitogen (PWM) response between the CFS and control groups. However, in control subjects, a significant association was observed between pokeweed mitogen responses and Rh(D) antigen status, whereas no similar association was measured in CFS patients. Rh(D)-negative control subjects had a significantly increased mitogen response compared with Rh(D)-positive subjects, whereas in CFS patients, no difference was found. It was concluded that future blood parameter and lymphocyte mitogen response studies in CFS patients should be controlled for sex and Rh status, respectively."

• 1997, A Preliminary Assessment of the Association of SCL-90-R Psychological Inventory Responses with Changes in Urinary Metabolites in Patients with Chronic Fatigue Syndrome

  Abstract - "A previous investigation of a cohort of 20 chronic fatigue syndrome (CFS) patients revealed an increased urinary excretion of an unusual metabolite, tentatively identified as amino-hydroxy-N-methyl-pyrrolidine (coded CFSUM1) and β-alanine, compared with 45 control subjects. The relative abundances of both CFSUM1 and β-alanine were positively associated with the core diagnostic symptoms of CFS and associated changes in amino and organic acid excretion. The psychological attributes of these CFS patients and controls were assessed in this study by using the Symptom Check List-90-revised (SCL-90-R) psychological inventory. The CFS patients had increases in the SCL-90-R. somatization, obsessive compulsive, depression, anxiety and phobic anxiety dimension scores. Nineteen of 20 CFS patients had somatization T-scores ≥ 63 (P < 0.0001), suggestive of a somatization disorder. Multiple regression analysis indicated that somatization was the most important SCL-90-R-defined dimension discriminating CFS from control subjects. Depression and anxiety were not found to be important inter-group determinants. The dimension scores were each related to specific changes in the urinary excretion of organic and amino acids, suggesting that each is biochemically distinct and has an organic basis. Cluster analysis of dimension profiles revealed that the profile with increased prevalence (P < 0.0001) in CFS patients was associated with increased excretion of CFSUM1 (P < 0.005) and had increases in somatization, obsessive compulsion and depression dimension scores. The PSDI as a measure of SCL-90-R symptom severity was positively correlated with CFSUM1 (model P < 0.003). CFSUM1 was also the primary correlate for the somatization dimension (model P < 0.0008), but was not associated with any other SCL-90-R-defined dimension. Another unidentified urinary metabolite, coded UM 15, was the primary correlate for depression (model P < 0.0004) and was associated with multiple dimension elevations by both cluster and logistic regression analysis; the excretion of this compound was unrelated to CFSUM1. These results indicated that, in this CFS cohort, the SCL-90-R defined psychological changes were strongly associated with changes in the biochemical homeostasis of patients, suggestive of an organic basis to CFS."

• 1996, Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome
• 1996, Preliminary determination of a molecular basis of chronic fatigue syndrome

Clinic location

Newcastle, Australia.

Online presence

• PubMed - Henry Butt

Learn more

• 2010, Gut Inflammation in Chronic Fatigue Syndrome
• 2000, Newcastle Team Lecture - Dr Henry Butt

See also

Bioscreen

References

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